NIH CRADA RSS Feed

Diagnostic Assays for the Detection of Thyroid Cancer

Thu, 06 Jun 2013 04:00:00 GMT

NIH scientists have developed two novel methods for distinguishing malignant from benign thyroid biopsy samples. Midkine and pleiotrophin, both low molecular weight growth factors, are over-expressed in many cancerous tissues. NIH researchers have developed ELISA assays to quantify the amount of midkine and pleiotrophin present in thyroid tissue samples. Levels of both growth factors are substantially higher in fine needle aspirates from thyroid cancers than from benign thyroid nodules. Application of this technique for the identification of thyroid cancer represents a first-in-class diagnostic for this disease.

Thyroid cancer represents a disease particularly amenable to improved methods of diagnosis. Thyroid nodules are very common in the adult population. To determine whether nodules are malignant, current practice involves obtaining a needle biopsy which is inspected microscopically. The resulting findings are subjective and often inconclusive, leading to unnecessary surgery. Therefore, there is a need for methods such as the present invention to improve diagnostic accuracy.

CRADA Opportunity: The National Institute of Child Health and Human Development, Section on Growth and Development, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize assays of biomarkers midkine, pleiotrophin in biopsy samples for cancer detection. For collaboration opportunities, please contact Charlotte McGuinness at mcguinnc@mail.nih.gov.

Improved Personalized Cancer Immunotherapy: Rapid Selection of Tumor-Reactive T Cells based on Expression of Specific Cell Surface Markers

Thu, 06 Jun 2013 08:00:00 GMT

Scientists at NIH have identified a process to select highly tumor-reactive T cells from a patient tumor sample based on the expression of four specific T cell surface markers: programmed cell death protein 1 (PD-1; CD279), 4-1BB (CD137), T cell Ig- and mucin-domain-containing molecule-3 (TIM-3), and/or lymphocyte activation gene 3 (LAG-3). After this enriched population of tumor fighting T cells, primarily tumor infiltrating lymphocytes (TIL), is selected and expanded to large quantities, it gets re-infused into the patient via an adoptive cell transfer (ACT) regimen. The key finding for this process is that the most tumor-reactive TIL found in a bulk population of cells obtained from a patient tumor sample reliably exhibit high expression of one or more of these four markers. By selecting cancer attacking TIL from a patient's tumor based on these markers prior to re-infusion, in vitro culture time is reduced to grow up the desired T cells and a more effective anti-cancer T cell product can be produced in comparison to previous TIL immunotherapy approaches.

This new method for selecting tumor-reactive T cells/TIL from tumor samples should help TIL immunotherapy become more GMP compliant and allow greater standardized of the TIL production process to enable more widespread utilization of this personalized cancer treatment approach outside of NIH.

CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize adoptive transfer of tumor infiltrating lymphocytes (TIL) for cancers other than melanoma. For collaboration opportunities, please contact Steven A. Rosenberg, M.D., Ph.D., at sar@nih.gov or 301-496-4164.

Methods for Producing Stem Cell-like Memory T cells for Use in T cell-based Immunotherapies

Wed, 22 May 2013 12:00:00 GMT

T cells currently employed for T cell-based immunotherapies are often senescent, terminally differentiated cells with poor proliferate and survival capacity. Recently, however, NIH scientists identified and characterized a new human memory T cell population with stem cell-like properties. Since these T cells have limited quantities in vivo, the scientists have developed methods by which high numbers of these cells can be generated ex vivo for use in T cell-based immunotherapies. Specifically, this technology describes a method for generating the stem cell-like memory T cells by stimulating naive T cells in the presence of inhibitors of GSK-3beta. It also describes a method for obtaining the stem cell-like memory T cells by sorting T cell lymphocytes using flow cytometry. These stem cell-like memory T cells display enhanced proliferation and survival upon transfer, have the multipotent capacity to generate all memory and effector T cell subsets and show increased anti-tumor activity in a humanized mouse tumor model. Consequently, the coupling of T cell receptor or chimeric receptor gene transfer with this method will enable the generation of a large number of memory stem cells with the desired specificity to effectively treat patients with cancer and chronic infectious diseases. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the use of T memory stem cells for T cell-based immunotherapies. For collaboration opportunities, please contact Luca Gattinoni at gattinol@mail.nih.gov or 301-451-6914, or Nicholas Restifo at restifo@nih.gov or 301-496-4904.

A Novel Human Antibody for Deploying CH2 Based Therapeutics

Wed, 22 May 2013 16:00:00 GMT

The subject invention describes a novel human antibody (anti-CH2 Fab m01m1) which could be used safely in vitro and in vivo for the detection of CH2 (Fc and IgG as well). More specifically, anti-CH2 Fab m01m1 recognizes a conformational epitope on CH2 so it can be used to monitor the conformational changes when CH2 is modified and mutated, as well as to select proper folded isolated CH2 domains. Thus, anti-CH2 Fab m01m1 is a powerful research reagent for developing the CH2-based novel therapeutics (nanoantibodies, nAbs) and for identifying several binders against various antigens from CH2-based libraries. CRADA Opportunity: The National Cancer Institute (NCI) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize A Novel Human Antibody for Deploying CH2 Based Therapeutics. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Novel Fusion Proteins for HIV Vaccine

Wed, 22 May 2013 20:00:00 GMT

The subject invention describes novel fusion proteins (CD4i antibody-HIV-1 envelop glycoprotein (gp120)) which can be used as 1) potential vaccine immunogens that could be more efficient than gp120 alone; 2) candidate therapeutics; and 3) research reagents for exploration of HIV-1 gp120 conformational flexibility, elucidation of mechanisms of virus entry, and evasion of immune responses. CRADA Opportunity: The National Cancer Institute (NCI) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Novel Fusion Proteins for HIV Vaccine. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

A Novel HIV-1 Entry Inhibitor

Thu, 23 May 2013 00:00:00 GMT

The subject invention describes a novel polypeptide comprising a single human CD4 domain (mD1.22) which is highly soluble and stable with significantly higher neutralizing activity and lower non-specific binding to human blood cell lines. More specifically, mD1.22 is highly promising for several applications due to its biophysical properties: 1) for conjugating with cytotoxic molecules for eradication of HIV-infected cells; 2) for generating multi-specific multi-valent HIV inhibitors with high neutralization potency and breadth, and relatively small molecular size; 3) for generating nanobio-sensors for rapid HIV detection; and 4) for studying the biological functions of CD4 in immune responses and HIV entry. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize A Novel HIV-1 Entry Inhibitor. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov.

Assay for Quantifying Fragile X Mental Retardation-1 Gene Product

Wed, 22 May 2013 04:00:00 GMT

The invention is directed to a fluorescence based assay to quantify the protein product of the Fragile X Mental Retardation-1 (FMR1) gene in a biological sample.

Fragile X syndrome (FXS) is an X-linked genetic disease that is responsible for intellectual disability and is also the most common single gene cause of autism. FXS is typically caused by loss of expression of the FMR1 gene, which codes for an RNA-binding protein called FMRP. FXS patients exhibit a wide spectrum of symptoms with varying degrees of cognitive and psychosocial impairment. The severity of these symptoms correlates well with the levels of FMRP present in the FXS patient. Because the FMR1 gene is silenced in varying degrees, the levels of FMRP in any particular FXS patient could vary greatly.

Scientists at NIDDK and NCATS have developed a sensitive, time resolved fluorescence based assay to quantify FMRP levels in a biological sample. Unlike other assays, the invention assay utilizes two highly-specific antibodies that bind to different sites of FMRP so as to enable precise and reliable quantification. Currently, there is no approved drug to treat FXS. The invention assay can be used as a high throughput screen to identify and evaluate candidate drugs. In addition, the invention assay can be used to assess and/or predict the severity of a patient's condition based on the amount of FMRP present. CRADA Opportunity: The National Center for Advancing Translational Sciences (NCATS) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Assay for Quantifying Fragile X Mental Retardation-1 Gene Product. For collaboration opportunities, please contact the NCATS Technology Development Coordinator at NCATSPartnerships@mail.nih.gov.

Pyruvate Kinase M2 Activators for the Treatment of Cancer

Fri, 10 May 2013 08:00:00 GMT

This technology describes a series of small-molecule activators of the pyruvate kinase M2 isoform (PK-M2).

Pyruvate kinase (PK) is a critical metabolic enzyme that catalyzes the last step of the glycolytic pathway. It exists in several isoforms with different patterns of tissue expression. One isoform, PK-M2, is expressed in cells with a high rate of nucleic acid synthesis, including most tumors, which makes this enzyme an attractive target for cancer therapy. PK-M2 can occur in either a tetrameric form or a dimeric form in proliferating cells; a high tetramer to dimer ratio leads to energy production, while a low ratio channels metabolites into synthetic processes. In tumor cells, oncoproteins induce dimerization of PK-M2, resulting in the inactive form of the protein and allowing synthesis of building blocks for cell proliferation. Activation of PK-M2 in these cells may prevent the buildup of metabolic intermediates and thereby stall tumor cell proliferation. Further, after embryonic development PK-M2 expression is primarily restricted to tumor cells, so specific activators of PK-M2 would be expected to affect only tumor cells, and would be less likely to be toxic in normal tissues.

Investigators at the National Center for Advancing Translational Sciences have discovered a series of small molecules that specifically activate the PK-M2 isoform and that may be useful for the treatment of cancer. These compounds are based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. CRADA Opportunity: The National Center for Advancing Translational Sciences (NCATS) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Pyruvate Kinase M2 Activators for the Treatment of Cancer. For collaboration opportunities, please contact the Office of Strategic Alliances at NCATSPartnerships@mail.nih.gov.

Enhanced Cancer Immunotherapy Using microRNA-155

Fri, 10 May 2013 12:00:00 GMT

Tumor immunotherapy is a promising approach for the treatment of cancer. However, current T cell-based immunotherapies are limited by the poor engraftment and functionality of the transferred T cells. Moreover, lymphodepleting regimens used to enhance engraftment and function of transferred tumor-reactive T cells are plagued by life-threatening side effects.

The scientists at the NIH recently discovered that the overexpression of microRNA-155 (miR-155) in tumor-reactive murine CD8+ T cells can enhance T cell proliferation and anti-tumor efficacy without lymphodepletion and exogenous cytokine administration. Consequently, using the miR155 overexpressing human CD8+ T cells could provide a safer, more effective T cell-based immunotherapy. This invention describes miR155 CD8+ T cell compositions and methods of using the miR155 CD8+ T cells to treat cancer through adoptive immunotherapy. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the use of microRNA-155 to enhance T cell-based immunotherapies. For collaboration opportunities, please contact Luca Gattinoni at gattinol@mail.nih.gov or 301-451-6914, or Nicholas Restifo at restifo@nih.gov or 301-496-4904. Click here to view the NCI collaborative opportunity announcement.

Retroviral Vector Packaging Cell Lines and Purification Methods for Gene Therapy

Fri, 10 May 2013 16:00:00 GMT

This invention relates to a novel gammaretroviral vector packaging cell line and method of producing gammaretroviral vectors suitable for gene therapy. The described vectors may contain the gibbon ape leukemia virus (GALV) envelope with a CD11D8 epitope tag enabling their purification on a monoclonal antibody conjugated column. These vectors have several advantages over existing systems, including a broader host range, higher infectivity, and lower potential for replication. Further, purification of retroviral vector particles via an epitope tag may remove cellular components and debris toxic to target cells and tissues, providing a safer method of delivery for patients receiving gene therapy. CRADA Opportunity: The National Institute of Mental Health is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Retroviral Vector Packaging Cell Lines and Purification Methods for Gene Therapy. For collaboration opportunities, please contact Suzanne L. Winfield, Ph.D. at winfiels@mail.nih.gov or 301-402-4324.

A Diagnostic Kit for Assessing Exposure or Infection by the Koala Family of Retroviruses

Fri, 10 May 2013 20:00:00 GMT

Inventors at the NIH have discovered a new family of infectious koala retroviruses that are correlated with the development of malignant neoplasias, including lymphomas and leukemias. This invention relates to a diagnostic kit for assessing exposure or infection by a koala retrovirus. The kit consists of specific primers and probes for the detection of three distinct subtypes of infectious koala retrovirus and may be useful in various species, including humans, primates, and koalas. Infectious koala retroviruses have been shown to infect human cells in culture, though the health implications in humans have not yet been fully determined. CRADA Opportunity: The National Institute of Mental Health is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize A Diagnostic Kit for Assessing Exposure or Infection by the Koala Family of Retroviruses. For collaboration opportunities, please contact Suzanne L. Winfield, Ph.D. at winfiels@mail.nih.gov or 301-402-4324.

Parvovirus B19 Vaccine

Wed, 08 May 2013 00:00:00 GMT

Parvovirus B19 (B19V) infection causes fifth disease, a disease characterized by rashes to the face and other parts of the body that primarily affects children. However, adults can also develop fifth disease and it can lead to more severe conditions. Patients that are immunocompromised, such as those who are HIV infected, organ transplant recipients, and cancer patients, can be particularly susceptible to more severe outcomes from B19V infection. Infection can also cause anemia and in pregnant women, it can lead to hydrops fetalis.

The subject technologies are expression vectors for the production of B19V VP1 and VP2 capsid proteins. Co-expression of the two proteins produce empty virus-like particles (VLPs) that can be used to develop a vaccine against parvovirus B19 and a packaging system for infectious B19V virus. Different expression vectors have been developed and optimized for expression in insects cells and more recently in mammalian cell lines such as 293, Cos7, Hela cells and 293T cells. CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the technology for producing Parvovirus B19 vaccine. For collaboration opportunities, please contact Cecilia Pazman, Ph.D. at pazmance@mail.nih.gov.

Stapled Peptides for Treatment of Cardiovascular Diseases and Inflammation

Tue, 07 May 2013 04:00:00 GMT

The invention is directed to small molecule mimetics of apolipoproteins that have an inter-helical hydrocarbon bond, which stabilizes helix formation.

Apolipoproteins facilitate the transport of lipids and cholesterol in the body. Mimetics of apolipoproteins have been used to treat cholesterol-related disorders. However, these mimetics are susceptible to degradation in biological fluids and as a result, their ability to bind cholesterol becomes diminished over time.

Scientists at NHLBI have devised methods to stabilize and improve the performance of apolipoprotein mimetic peptides, using a modified hydrocarbon chain (“stapled apolipoproteins”). These stapled apolipoproteins are superior to singular apolipoproteins in that they are more resistant to enzymatic degradation and efflux a greater amount of cellular cholesterol.

Stapled apolipoproteins can be used in the treatment of cardiovascular diseases, particularly for treatment of atherosclerosis. CRADA Opportunity: The NHLBI Lipoprotein Metabolism Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Hydrocarbon-stapled Apolipoprotein Peptide Mimetics for the Treatment of Cardiovascular Diseases and Inflammation. For collaboration opportunities, please contact Denise Crooks, Ph.D. at crooksd@nhlbi.nih.gov.

Induced Pluripotent Stem Cells Generated Using Lentivirus-based Reprogramming

Tue, 07 May 2013 08:00:00 GMT

Five human induced pluripotent stem cells (iPSC) lines are generated using lentivirus-based reprogramming technology. These lines are pluripotent, meaning they have the potential to differentiate into all cells in the body, and theoretically can proliferate/self-renew indefinitely. The iPSC lines are: NC1 (derived from female's fibroblasts), NC2 (derived from female's fibroblasts ), NC3 (derived from male's HUVECS), NC4 (derived from male's fibroblasts) and NC5 (derived from female's fibroblasts). Further details of these cells are available upon request. NC1 uses a retrovirus delivery system incorporating the following vectors: pMIG-hKLF4, pMIG-hOCT4, pMIG-hSOX2, and MSCV h c-MYC IRES GFP. NC2-NC5 use the hSTEMCCA-loxP lentivirus delivery system (a gift from Dr. Gustavo Mostoslavsky). These cell lines will be useful for studies related to stem cell biology, understanding diseases, potential cell therapies, and small molecule screening. CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Induced Pluripotent Stem Cells. For collaboration opportunities, please contact Denise Crooks at 301-435-0103.

VEGF-B as a Therapeutic Agent for Neurodegenerative Disease

Tue, 07 May 2013 12:00:00 GMT

This technology identifies vascular endothelial growth factor-B (VEGF-B) as a potent inhibitor of apoptosis in neuronal and other types of cells, and highlights its ability to rescue these cells from apoptosis in the brain and retina. Members of the VEGF family of proteins are noted for their angiogenic and blood vessel permeabilizing abilities. Some members of this family, such as VEGF-A, may promote neurogenesis; however, the neuroprotective effects are accompanied by inherent angiogenic and vessel permeabilizing activities, which make VEGF-A treatment unsuitable for clinical use as neuroprotective agents. The inventor has recently discovered that unlike the other VEGF family members, the neuroprotective effects of VEGF-B are not associated with undesired angiogenesis or increased blood vessel permeability, but rather through inhibiting apoptosis via suppressing the expression of the apoptotic/cell death related genes (1). This discovery, that the use of VEGF-B can protect endangered neurons from death and avoid the undesirable effects associated with other VEGF family members, makes it a promising candidate for the treatment of neurodegenerative and other diseases that involve neuronal impairment and/or excessive apoptosis, such as muscular dystrophy, stroke, brain injury, myocardial infarction, ischemic renal damage, etc.

In-vivo trials have already demonstrated the efficacy of VEGF-B as a therapeutic agent. VEGF-B has shown efficacy in mouse models suffering from optic nerve crush injury (ONC). ONC induces the apoptotic death of retinal ganglion cells (RGCs) in the retina. However, intravitreal administration of a single dose of the VEGF-B protein significantly restored the number of RGCs by 1.7 fold, demonstrating the potential use of the protein in treating degenerative ocular diseases, such as glaucoma. Similar results were obtained when exogenous administration of VEGF-B to the brain cortex was shown to significantly reduce ischemia-induced stroke volume and to protect neurons from apoptosis in the brain. Further, intracerebroventricular injection of VEGF-B in mutant knockout mice lacking the gene for VEGF-B (VEGFB-KO) has caused a complete reversal of neuronal impairment and restored neurogenesis back to normal levels. CRADA Opportunity: The National Eye Institute, NIH, Office of Scientific Director, Unit of Retinal Vascular Neurobiology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize VEGF-B as a therapeutic agent in treating various types of degenerative (neural, vascular, muscular, etc) diseases, and to study the molecular and cellular mechanisms involved. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

User-friendly, Powerful Software for Analyzing ChIP-Seq Data

Tue, 23 Apr 2013 16:00:00 GMT

The present invention provides a user-friendly software, called PAPST (Peak Assignment and Profile Search Tool for ChIP-Seq), for bench scientists to work with ChIP-Seq data in seconds, allowing the scientists to screen genes against multiple genomic features with ease and efficiency previously not realized. Furthermore, PAPST may be used to identify genes of special significance in a wide variety of biological and biomedical fields, which could lead the discovery of disease-associated genes and the development of therapeutic methods for human diseases. Lastly, this powerful, easy-to-use software does not require any special computation expertise. CRADA Opportunity: The Biodata Mining & Discovery Section of the National Institute of Arthritis and Musculoskeletal and Skin Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize PAPST (Peak Assignment and Profile Search Tool for ChIP-Seq). For collaboration opportunities, please contact Hong-Wei Sun at 301-496-0016 or sunh1@mail.nih.gov.

Urine-based Diagnostic Assay for the Early Detection of Cancer

Tue, 23 Apr 2013 20:00:00 GMT

NIH scientists have identified a panel of metabolite biomarkers capable of predicting the onset of cancer with an accuracy approaching 100%. Concerted changes in the levels of select amino acid, nucleic acid and methylation metabolites in the urine of mice strongly correlated with tumor formation and reflected the progressive derangement in their underlying biochemical pathways. Researchers have developed high-throughput screening methodology to quantify the levels of these metabolites in biological samples for the purposes of assessing cancer risk, determining disease prognosis and monitoring response to therapy. While applicable to many cancers, use of this technology for the detection of colorectal cancer represents a first-in-class diagnostic for this particular disease.

Despite therapeutic advances, colorectal cancer remains a significant clinical burden in terms of morbidity and mortality. Early detection is a key predictor of treatment outcome; however, current diagnostic methods are unsuitable for widespread implementation. The ability to analyze noninvasively obtained patient samples in a high-throughput manner suggests that this technology is well positioned to serve as a population-level screening tool for the early detection of many cancers, including, colorectal. CRADA Opportunity: The National Cancer Institute, Laboratory of Metabolism, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize a non-invasive assay for the detection of colorectal cancer. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov.

Device for Non-Surgical Tricuspid Valve Annuloplasty

Wed, 24 Apr 2013 00:00:00 GMT

This is a non-surgical tricuspid annuloplasty to treat functional tricuspid valve regurgitation, meaning regurgitation with intact valve leaflets. The device is delivered using novel catheter techniques into the pericardial space and positioned along the atrioventricular groove. A compression member is positioned along the tricuspid annular free wall and tension applied through a variably-applied tension element. In the best embodiment, the compression member has an M shaped portion with at least two inflection points between the segments of difference curvatures. CRADA Opportunity: The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize technologies for functional tricuspid valve regurgitation. For collaboration opportunities, please contact Peg Koelble at koelblep@nhlbi.nih.gov.

Novel Tocopherol and Tocopheryl Quinone Derivatives as Therapeutics for Lysosomal Storage Disorders

Tue, 23 Apr 2013 04:00:00 GMT

Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes. These molecules by themselves or in combination with Cyclodextrins (CDs) increase intracellular Ca2+ and enhance exocytosis. Also, the treatment with these compounds reduced the pathological changes in the ultrastructure of LSD cells as observed using electron microscopy analysis. The inventors also found that there is a synergy between CDs and the new tocopherol analogues when tested on the NPC cells and cells from six other lysosomal storage diseases including Wolman, Niemann Pick Type A, Farber, TaySachs, MSIIIB and CLN2 (Batten) diseases. These new tocopherol analogues are as good or better than natural occurring tocopherols and tocotrienols in reducing cholesterol accumulation in several LSDs. CRADA Opportunity: The National Center for Advancing Translational Sciences (NCATS) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Novel Tocopherol and Tocopheryl Quinone Derivatives as Therapeutics for Lysosomal Storage Disorders. For collaboration opportunities, please contact the NCATS Technology Development Coordinator at NCATSPartnerships@mail.nih.gov.

Novel Methods for Generating Retinal Pigment Epithelium Cells from Induced Pluripotent Stem Cells

Tue, 23 Apr 2013 08:00:00 GMT

High efficiency methods for producing retinal pigment epithelial cells (RPE) from induced pluripotent stem cells (iPSCs) are disclosed. The RPE is a polarized monolayer in the vertebrate eye that separates the neural retina from the choroid, and performs a crucial role in retinal physiology by forming a blood-retinal barrier and closely interacting with photoreceptors to maintain visual function. Many ophthalmic diseases, such as age-related macular degeneration, are associated with a degeneration or deterioration of the RPE. The iPSCs are produced from somatic cells, including retinal pigment epithelial cells, such as fetal RPE. These methods involve producing embryoid bodies from human iPSCs, culturing the embryoid bodies using specific media to induce differentiation into RPE and growing the differentiated RPE cells in a defined media to generate human RPE cells. The investigators also developed methods for detecting RPE cells and authenticating RPE cells; determining agents that can affect the production of RPE cells from an iPSC; and identifying an agent that can increase RPE survival in response to a proteo toxic insult or stress. The novel methods and RPE cells disclosed here can be useful for both pre-clinical and clinical studies involving RPE. CRADA Opportunity: The National Eye Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize iPSC to RPE differentiation protocol, its clinical, screening, and translational applications. For collaboration opportunities, please contact Alan Hubbs, Ph.D. at hubbsa@mail.nih.gov. Click here to view the NEI collaborative opportunity announcement.

Zirconium-89 PET Imaging Agent for Cancer

Tue, 23 Apr 2013 12:00:00 GMT

This technology is a new generation of rationally designed chelating agents which improve the complexation of Zirconium-89 for PET imaging of cancers. The technology uses cyclic or acyclic chelators made of 4 hydroxamate donors groups for improved stability compared to the currently used natural product siderophore desferrioxamine B (DFB), a chelator that consists of only 3 hydroxamate donors that fails to saturate the coordination sphere of Zr(IV). DFB, which has been the object of many pre-clinical and clinical studies exhibits insufficient stability resulting in progressive radioisotope accumulation in bone once injected that can contribute to toxicity and increased background. The new chelators described in this invention have shown improved kinetic inertness compared to DFB with stability up to 90% after 7 days compared to 28% for DFB. In association with an adequate targeting agent such as an antibody, toxicity to the bone can be reduced and images with better contrast can be obtained with these new chelators. CRADA Opportunity: The Radioimmune & Inorganic Chemistry Section, ROB, CCR, NCI, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Zirconium-89 chelation technology for ImmunoPET imaging and other applications. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Peptide Inhibitor of Cyclin Dependent Kinase 4 (CDK4) Derived from MyoD

Thu, 18 Apr 2013 16:00:00 GMT

This invention pertains to cell cycle regulation and the activity of the G1 cyclin-dependent kinase 4 (CDK4). The invention describes a 15 amino acid peptide and variants thereof derived from muscle determination factor, MyoD, which is an inhibitor of the CDK4. CDK4 is one of a number of cyclin-dependent kinases which control progression through the cell cycle through their ability to phosphorylate particular substrates at the correct phase of the cell cycle. CDK4 has been shown to be involved in cell cycle control through its ability to regulate the activity of the retinoblastoma protein, pRb, an activator of genes essential for cell division.

Inhibitors of the cyclin-dependent kinases, such as the peptides described in this invention, prevent cell cycle progression and induce cells to exit the cell cycle into the Go state. The peptides described in this invention prevent the phosphorylation of pRb by CDK4, an obligate step for entry into the cell cycle. Osteosarcomas and habdosarcomas are two types of tumors known to over-express pRb. The inhibitor described in this invention may be useful in treating these cancers or other diseases which have been specifically linked to over-expression of active pRb. CRADA Opportunity: The National Cancer Institute’s Laboratory of Biochemistry and Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the described cdk4 inhibitory peptides or equivalent peptide mimetics. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Lentiviral Vectors with Dual Fluorescence/Luminescence Reporters

Mon, 08 Apr 2013 20:00:00 GMT

Twelve lentiviral vectors that express both fluorescent and luminescent markers as a single fusion protein under various gene promoters were constructed. Vectors have been developed previously to monitor tumors or tumor cells via bioluminescence or fluorescence alone. However, bioluminescence is not sensitive enough to sort individual tumor cells and fluorescence cannot be used effectively to view internal tumors. By combining the two reporters into a single fusion protein, the tumor can be effectively visualized within the animal as well as sorted from non-tumor cells for post-necropsy experiments. The added advantage of bioluminescent visualization allows for in vivo experiments that more closely simulate the biological development of tumors in organs rather than at the surface of the skin. Additionally, since twelve different vectors with different gene promoters were developed, they can be tested in individual tumor models to find the best vector for visualizing that particular tumor cell line. The vectors are able to sustain long-term expression of both visualization markers, depending on the cell type and promoter in each vector. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize dual luminescent/fluorescent vectors. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

CpG Oligonucleotides Treatment to Prevent Chemotherapy-Induced Pulmonary Toxicity

Fri, 05 Apr 2013 00:00:00 GMT

Bleomycin (BLM) is a chemotherapy agent used to treat multiple types of cancer, but its side effects are life threatening for some patients. About 20% of patients undergoing BLM chemotherapy develop interstitial pneumonitis which may develop to life threatening fibrosis. In such cases, BLM chemotherapy cannot be continued.

This invention identifies a method of pre-treatment using immunostimulatory CpG Oligonucleotide (ODN) molecules to prevent chemotherapy-induced pulmonary toxicity. Administration of certain ODN molecules induces inflammation via stimulation of inflammatory genes (Toll-like receptor 9/TLR9). This stimulation is subsequently down-regulated. This technology makes use of this counter regulatory mechanism to reduce the side effects of chemotherapy agents, such as BML. A properly timed pre-administration of ODN molecules, prior to BML therapy, prevents the lethal side effect of BLM-induced pulmonary inflammation and down-regulates promoters of BLM toxicity (IL-17A and TGF-beta1). Because toxicity from pulmonary inflammation is a side effect limiting use of many chemotherapeutic agents and ODN molecules are relatively inexpensive and have a favorable safety profile, this technology may be useful to improve treatment protocols for many chemotherapy agents. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize CpG oligonucleotides for use to down-modulate inflammatory reactions. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Highly Potent and Selective Deubiquitinating Enzyme Inhibitor

Thu, 04 Apr 2013 04:00:00 GMT

Available for licensing are inhibitors that target the USP1/ UAF1 deubiquitinating enzyme (DUB) complex. The FDA approval and commercial success of Velcade®, a small molecule proteasome inhibitor, has established the ubiquitin-proteasome system (UPS) as a valid target for anticancer treatment. However, proteasome inhibitors in general suffer from a narrow therapeutic index and acquired resistance. A promising alternative to proteasome inhibition has been to target the enzymes upstream of proteasome-mediated protein degradation, i.e. the ubiquitin conjugation and deconjugation, to generate more specific, less toxic therapeutic agents. The investigators have developed small molecules that target the USP1/ UAF1 DUB complex that acts upstream of UPS and has been implicated in the DNA damage response. These compounds are the most potent and selective DUB inhibitors reported to date. Moreover, the inhibitors act synergistically with cisplatin, a DNA damaging anti-cancer drug, to overcome chemoresistance and enhance cytotoxicity. These results suggest the inhibitors may also improve the efficacy and potency of other commonly prescribed chemotherapeutic agents that are known to induce DNA damage. CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this invention. For collaboration opportunities, please contact Lili Portilla at lili.portilla@nih.gov.

Combination Chemotherapeutics for the Treatment of Chordoma

Tue, 12 Mar 2013 08:00:00 GMT

Utilizing high-throughput screening methodology, NIH scientists have identified two classes of clinically-available drugs, proteasome inhibitors and topoisomerase inhibitors, that synergize to promote chordoma cell death. Moreover, use of the two-part chemotherapeutic regimen in animal models effectively suppressed the growth of chordoma cells and resulted in significant tumor regression. Currently, no chemotherapeutic agents have been approved for the treatment of chordoma. Using FDA approved drugs in a combination therapeutic regimen will help expedite the availability of a therapeutic for chordoma.

Chordoma is a rare form of bone cancer that arises within the skull, sacrum or bony spine. Surgical resection and radiation therapy are the current standards-of-care; however, post-treatment complications remain significant and neither modality is effective for the control of metastatic tumors. CRADA Opportunity: The National Center for Advancing Translational Sciences, Division of Pre-Clinical Innovation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Combination Chemotherapeutics for the Treatment of Chordoma. For collaboration opportunities, please contact Lili M. Portilla, MPA at lilip@nih.gov.

Ketone Bodies to Protect Tissues from Damage by Ionizing Radiation

Tue, 12 Mar 2013 12:00:00 GMT

The invention relates to methods of using ketogenic compounds to protect against the adverse effects of radiation exposure, including ionizing radiation tissue damage. NIH inventors have discovered that ketone esters can be used to reduce tissue damage if administered before or after exposure to radiation. Specifically, the invention relates to esters and oligomers of (R)-3-hydroxybutyrate that are capable of elevating blood levels of (R)-3-hydroxybutyrate and acetoacetate to sufficient levels to reduce cell death caused by radiation-induced damage of DNA and RNA. The development of effective radioprotectant molecules such as these is of great importance in reducing tissue damage following intentional or accidental radiation exposure. This discovery can also increase the therapeutic efficacy of radiation therapies by protecting non-target tissues from incidental radiation damage. CRADA Opportunity: The NIAAA is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Ketone Bodies to Protect Tissues from Damage by Ionizing Radiation. For collaboration opportunities, please contact Peter B. Silverman, Ph.D., J.D. at psilverm@mail.nih.gov or 301-402-6966.

Brachyury-directed Vaccine for the Prevention or Treatment of Cancers

Thu, 21 Feb 2013 17:00:00 GMT

Tumor invasion and metastasis are the primary drivers of cancer-related mortality. Therapies that have an ability to specifically target invasive and/or metastatic cells are anticipated to have a significant impact in the clinical management of advanced cancers.

Researchers at the NIH have developed a vaccine technology that stimulates the immune system to selectively destroy metastasizing cells. Brachyury, a master transcription factor that governs the epithelial-mesenchymal transition, was shown to be significantly overexpressed in primary and metastasizing tumors relative to normal human tissues. Stimulation of T cells with the Brachyury peptide promoted a robust immune response and the targeted lysis of invasive tumor cells. Brachyury overexpression has been demonstrated in a range of human tumors (breast, lung, colon and prostate, among others) suggesting that a therapeutic vaccine derived from this technology would be broadly applicable for the treatment of cancer. CRADA Opportunity: The National Cancer Institute Laboratory of Tumor Immunology and Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Brachyury-directed cancer vaccine technology. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Novel Host Target for Treatment of Hepatitis C Virus Infection

Thu, 21 Feb 2013 22:00:00 GMT

The subject technology is a newly discovered Interferon-lambda 4 (IFNL4) protein found through analysis of genomic data derived from primary human hepatocytes, molecular cloning and functional annotation. The IFNL4 protein is related to but distinct from other know IFNs and its expression is inducible in conditions that mimic viral infection. Preliminary studies indicate that this protein may play a role in impaired natural and treatment induced clearance of HCV. These findings suggest that the protein can potentially be a new target for treating HCV infection. CRADA Opportunity: The NCI Division of Cancer Epidemiology & Genetics, Laboratory of Translational Genomics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize development of tools for detection of IFNL4 mRNA and protein and modulation of its function. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Novel Diagnostic Marker for Prediction of Clearance of Hepatitis C Virus Infection

Fri, 22 Feb 2013 03:00:00 GMT

One of the unfortunate aspects of hepatitis C virus (HCV) infection is that the majority of infected individuals will develop a chronic HCV infection. The current treatment for HCV infection involves direct acting antiviral drugs, such as HCV protease inhibitors, with or without pegylated IFN-alpha/ribavirin. Not all patients respond to treatments and the treatments themselves can cause severe adverse effects. The subject invention (IFNL4-deltaG) is a novel genetic polymorphism in the newly discovered Interferon Lambda 4 (IFNL4) gene, which is located near the IFNL3 (former IL28B) gene. The IFNL4-deltaG polymorphism can predict the likelihood of whether or not a patient will respond to treatment of HCV and, possibly, of other diseases treated with IFN-alpha (or other interferons). In particular, IFNL4-deltaG was found to be a better predictor of clinical outcome for IFN-alpha based treatment in people of African descent than the currently available diagnostic test (‘IL28B’ genotype, defined by rs12979860 located within first intron of IFNL4). The predictive value of the IFNL4-deltaG polymorphism for response to IFN-alpha based treatment in HCV-infected Caucasians and Asians is comparable to current diagnostics. In addition, IFNL4-deltaG can predict the likelihood of a whether a person who is acutely infected with HCV infection will spontaneously clear the infection or develop chronic infection. As with treatment outcome, among individuals of African ancestry, genotype for IFNL4-deltaG is a better predictive marker for spontaneous clearance of HCV than ‘IL28B’ genotype, while providing similar predictive value in individuals of European or Asian descent. CRADA Opportunity: The NCI Division of Cancer Epidemiology & Genetics, Laboratory of Translational Genomics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize development of a gene-based test to be used in the clinic. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

A High-Throughput Assay for Detection and Monitoring of Endocrine-Disrupting Chemicals in Water Sources

Thu, 21 Feb 2013 08:00:00 GMT

This technology describes a high-throughput, fluorescence-based method to detect endocrine-disrupting chemicals (EDCs) in water sources.

There is growing awareness that a wide variety of synthetic and natural compounds that may lead to adverse health effects are present in water sources, such as streams, wells, and ground water; however, these compounds are often difficult to measure and thus are not commonly monitored. Even low concentrations of these compounds are of concern, as they may have biological effects at concentrations of parts per billion (PPB) or less. The presence of EDCs in the environment, in particular, is under examination for potential adverse effects on human health and on wildlife, such as cancer, immune suppression, impaired fertility, and increased incidence of diabetes and obesity.

Inventors at NCI have discovered a novel assay methodology for detecting endocrine EDCs in contaminated water. The assay utilizes fluorescently-labeled nuclear receptors in a high-throughput, cell-based format, and has the capability to detect very low concentrations of EDCs in water or other liquid samples. The inventors have already demonstrated proof of concept for this technology by using this assay to test for the presence of glucocorticoid and androgen receptor disruptors in water samples from 14 U.S. states, and also plan future studies for other types of EDCs. A product or service based on this technology could fulfill an unmet need for a high-throughput, rapid method for screening water samples for contaminants with potential endocrine-disrupting effects. CRADA Opportunity: The NCI Laboratory of Receptor Biology & Gene Expression is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Detection and Monitoring of Endocrine-Disrupting Chemicals in Water Sources. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Novel Vaccine for Prevention and Treatment of Chlamydia Infection

Thu, 21 Feb 2013 13:00:00 GMT

The invention provides novel vectors, attenuated pathogens, compositions, methods and kits for preventing and/or treating chlamydia infections.

Chlamydia trachomatis is an obligate intracellular human pathogen with a unique biphasic developmental growth cycle. It's the etiological agent of trachoma, the world's leading cause of preventable blindness and the most common cause of bacterial sexually transmitted disease. C. trachomatis isolates maintain a highly conserved plasmid and naturally occurring plasmidless clinical isolates are rare, implicating its importance in chlamydial pathogenesis. Understanding the plasmid's role in chlamydial pathogenesis at a molecular level is an important objective for the future control of chlamydial infections. The NIAID inventor had studied chlamydia strains in both non-human primate and murine infectious models providing evidence that plasmids play an important role in chlamydial pathogenesis. In addition, the study results of macaque model of trachoma supports the use of plasmid-deficient organisms as novel live-attenuated chlamydial vaccines. CRADA Opportunity: The NIAID Laboratory of Intracellular Parasites is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize chlamydia vaccine. For collaboration opportunities, please contact Harlan D. Caldwell, Ph.D. at hcaldwell@niaid.nih.gov.

Modified Peptide Nucleic Acids (PNAs) for Detection of DNA or RNA and Identification of a Disease or Pathogen

Thu, 21 Feb 2013 18:00:00 GMT

The NIH announces a novel method for fast, simple, and accurate detection of nucleic acids outside the modern laboratory. Nucleic acid testing is highly specific and often provides definitive identification of a disease or pathogen. Methods to detect nucleic acid sequences and identify a disease or pathogen are dominated by PCR, but applying PCR-based techniques in remote settings is challenging. Researchers at the NIH have developed a universal, colorimetric, nucleic acid-responsive diagnostic system that uses two short peptide nucleic acid (PNA) probes and does not rely on PCR. The design of a cyclopentane-modified surface probe and a biotin-containing reporter probe allows excellent DNA and RNA detection. NIH researchers have specifically demonstrated this technology's suitability for early detection of HIV RNA or anthrax DNA. CRADA Opportunity: The NIDDK is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Modified Peptide Nucleic Acids (PNAs) for Detection of DNA or RNA. For collaboration opportunities, please contact Cindy K. Fuchs, J.D. at Cindy.Fuchs@nih.hhs.gov or 301-451-3636.

Silica-Coated Nanodiamonds for Imaging and the Delivery of Therapeutic Agents

Thu, 21 Feb 2013 23:00:00 GMT

NIH investigators invented a robust and easily implemented method of synthesizing silica-coated nanodiamonds for imaging and therapeutic applications. A patent estate covering these methods is offered for licensing to commercial entities. The method generally includes coating nanodiamonds with a silica precursor, e.g., tetraethylorthosilicate (TEOS), inside liposomes. The liposomes are then removed to yield a final product that is stable, monodisperse, and easy to functionalize. CRADA Opportunity: The NHLBI Laboratory of Single Molecule Biophysics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize fluorescent nanodiamonds for use as in vivo and in vitro optical tracking probes. For collaboration opportunities, please contact Keir C. Neuman, Ph.D. at neumankc@mail.nih.gov or 301-496-3376. Click here to view the collaborative opportunity announcement for this joint NHLBI/NCI technology.

Background-Free Fluorescent Nanodiamond Imaging

Fri, 22 Feb 2013 04:00:00 GMT

Available for licensing and commercial development are intellectual property rights covering a method of imaging a biological specimen (e.g., human tissue) using fluorescent nanodiamonds implanted into the subject of interest, applying a magnetic field to said subject and producing a resultant image by a net juxtaposition of a second acquired image. This process suppresses the background and permits selective imaging of the nanodiamonds in the presence of background fluorescence that exceeds the signal from the nanodiamonds. Another aspect of the invention provides an imaging method in which the resulting image is acquired by applying time-varying magnetic fields using one or more secondary image averaged against the first. The technique relies on imposing a small (~100 Gauss) magnetic field on the sample of interest during optical imaging combined with post-processing of the acquired images to remove the background. This technology can readily be added onto any commercial optical imaging platform to achieve background-free images of the nanodiamonds in a biological specimen. CRADA Opportunity: The NHLBI Laboratory of Single Molecule Biophysics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize background-free imaging of fluorescent nanodiamonds for in vivo and in vitro applications. For collaboration opportunities, please contact Keir C. Neuman, Ph.D. at neumankc@mail.nih.gov or 301-496-3376.

Software to Improve the Quality of Microscopy Images

Thu, 21 Feb 2013 09:00:00 GMT

Available for licensing and commercial use is software based on an iterative deconvolution procedure that recovers images that have been blurred by a known point spread function. The software provides superior results when multiple independent observations of the same specimen are obtained. An example of such observations might be the multiple views of a specimen collected by a selective illumination plane microscope (SPIM). By using the blurring function and observations (raw images) corresponding to each view in sequential order through the iteration loop, the resulting output contains higher resolution, contrast, and signal than would result if any single observation alone was used, or if the output from single deconvolution operations on each image are combined, e.g. by averaging. In its current form, the software has been tested on the Richardson-Lucy deconvolution (RLD) procedure. Preliminary data indicate that the algorithm provides an isotropic resolution of 350 nm, greatly improving the raw data (lateral resolution 0.5 microns, axial resolution 1.5 microns) on nematode embryos. In vivo data illustrating the power of the algorithm are available upon request. CRADA Opportunity: The NIBIB Section on High Resolution Optical Imaging is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize our algorithm, especially with respect to multiview microscopes. For collaboration opportunities, please contact Hari Shroff at hari.schroff@nih.gov.

Oral Shigellosis Vaccine

Tue, 05 Feb 2013 14:00:00 GMT

This application claims a Salmonella typhi Ty21a construct comprising a Shigella sonnei O-antigen biosynthetic gene region inserted into the Salmonella typhi Ty21a chromosome, where heterologous Shigella sonnei form 1 O-antigen is stably expressed together with homologous Salmonella typhi O-antigen. The constructs of this invention elicit immune protection against virulent Shigella sonnei challenge, as well as Salmonella Typhi challenge. Also claimed in this application are methods of recombineering a large antigenic gene region into a bacterial chromosome.

Bacillary dysentery and enteric fevers continue to be important causes of morbidity in both developed and developing nations. Shigella cause greater than one hundred and fifty million cases of dysentery and enteric fever occurs in greater than twenty-seven million people annually. Currently, there is no licensed vaccine to prevent the occurrence of shigellosis. Increasing multiple resistance in Shigella commonly thwarts local therapies. CRADA Opportunity: The FDA Center for Biologics Evaluation and Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize oral Shigellosis vaccine. For collaboration opportunities, please contact Dr. Dennis J. Kopecko at dennis.kopecko@fda.hhs.gov or 301-661-8839.

Live Oral Shigella dysenteriae Vaccine

Tue, 05 Feb 2013 19:00:00 GMT
This application claims a Salmonella typhi Ty21a construct comprising a Shigella dysenteriae O-specific polysaccharide (O-Ps) inserted into the Salmonella typhi Ty21a chromosome, where heterologous Shigella dysenteriae serotype 1 O-antigen is stably expressed together with homologous Salmonella typhi O-antigen. The constructs of this invention elicit immune protection against virulent Shigella dysenteriae challenge, as well as Salmonella typhi challenge. Also claimed in this application are methods of making the constructs of this invention and methods for inducing an immune response.

Shigella cause millions of cases of dysentery every year, which result in about seven hundred thousand deaths worldwide. Shigella dysenteriae serotype 1, one of about forty serotypes of Shigella, causes a more severe disease with a much higher mortality rate than other serotypes. There are no licensed vaccines available for protection against Shigella. The fact that many isolates exhibit multiple antibiotic resistance complicates the management of dysentery infections. CRADA Opportunity: The FDA Center for Biologics Evaluation and Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize combination typhoid-shigellosis oral vaccine. For collaboration opportunities, please contact Dr. Dennis J. Kopecko at dennis.kopecko@fda.hhs.gov or 301-661-8839.

DNA Promoters and Anthrax Vaccines

Wed, 06 Feb 2013 00:00:00 GMT
Currently, the only licensed vaccine against anthrax in the United States is AVA BioThrax®, which, although efficacious, suffers from several limitations. This vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires a cold chain for storage, and in many cases has been associated with adverse effects.

This application claims a modified B. anthracis protective antigen (PA) gene for optimal expression and stability, linked it to an inducible promoter for maximal expression in the host, and fused to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) on a low-copy-number plasmid. This plasmid was introduced into the licensed typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was found to be genetically stable. Immunization of mice with three vaccine doses elicited a strong PA-specific serum immunoglobulin G response with a geometric mean titer of 30,000 (range, 5,800 to 157,000) and lethal-toxin-neutralizing titers greater than 16,000. Vaccinated mice demonstrated 100% protection against a lethal intranasal challenge with aerosolized spores of B. anthracis 7702. CRADA Opportunity: The FDA Center for Biologics Evaluation and Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize oral anthrax vaccine. For collaboration opportunities, please contact Dr. Dennis J. Kopecko at dennis.kopecko@fda.hhs.gov or 301-661-8839.

Human Melanoma Metastasis Cell Lines Harboring TRRAP, GRIN2A, and PLCB4 Mutations

Mon, 04 Feb 2013 05:00:00 GMT
Researchers at the NIH have identified several novel somatic (e.g., tumor-specific) alterations, many of which have not previously been known to be genetically altered in tumors or linked to melanoma. In particular, the researchers identified a recurrent “hotspot” mutation in the transformation/transcription domain-associated protein (TRRAP) gene, identified the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene as a highly mutated in melanoma, and have shown that the majority of melanoma tumors have alternations in genes encoding members of the glutamate signaling pathway, such as phospholipase C, beta 4 (PLCB4). Therefore, this technology not only provides a comprehensive map of genetic alterations in melanoma, but has important diagnostic and therapeutic applications.

Available for licensing are several melanoma cell lines that harbor TRRAP, GRIN2A, and PLCB4 mutations. These cell lines provide useful and efficient tools for studying melanoma and can be used in the development of specific therapeutics for patients harboring these mutations. Specifically, these cell lines could be used to develop inhibitors to limit tumor growth and further understand melanoma and the biology of these genes. CRADA Opportunity: The NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Claire Driscoll, Director, NHGRI Technology Transfer Office, at cdriscol@mail.nih.gov or 301-594-2235.

Human Melanoma Metastasis Cell Lines Harboring MITF Mutations

Mon, 04 Feb 2013 10:00:00 GMT
Researchers at the NIH have found recurrent somatic mutations in the microphthalmia-associated transcription factor (MITF). Previous studies have linked the MITF pathway to the progression of melanoma, however, little is known about somatic gene mutations in the MITF pathway that could contribute to this progression. The NIH researchers evaluated primary and metastatic melanoma samples for the presence of somatic mutations in two genes of the MITF pathway, MITF and SRY (sex determining region Y)-box 10 (SOX10). They identified 16 previously unidentified somatic mutations in these genes. These studies suggest that MITF and SOX10 genes could be used as diagnostic markers in human metastatic melanoma. Consequently, these cell lines could be used to further investigate the effects of MITF and SOX10 in melanoma and to develop therapeutics targeting this gene and protein. CRADA Opportunity: The NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Claire Driscoll, Director, NHGRI Technology Transfer Office, at cdriscol@mail.nih.gov or 301-594-2235.

Human Melanoma Metastasis Cell Lines Harboring GRM3 Mutations

Mon, 04 Feb 2013 15:00:00 GMT
Using exon capture and next generation sequencing approaches to analyze the entire G protein coupled receptor (GPCR) gene family in melanoma, the researchers at the NIH have identified several novel somatic (e.g., tumor-specific) alterations. GPCRs play an integral part in regulating physiological functions and the importance of these molecules is evident by the fact that approximately half of the current FDA approved therapeutics target GPCRs or their direct downstream signaling components. Many of the GPCR gene mutations identified by the NIH researchers were mutated in a large portion of melanoma patients and already have inhibitors, the most notable being the Glutamate Receptor Metabotropic 3 (GRM3) mutation which could be functionally signification for melanoma tumorigenesis.

Available for licensing are several melanoma cell lines that harbor GRM3 mutations. These cell lines provide useful and efficient tools for studying melanoma and can be used in the development of specific inhibitors of GRM3 as well as the pathway it activates, mitogen-activated protein kinase (MEK), for the treatment of melanoma patients with these mutations. CRADA Opportunity: The NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Claire Driscoll, Director, NHGRI Technology Transfer Office, at cdriscol@mail.nih.gov or 301-594-2235.

Mutations in the G Protein Coupled Receptor (GPCR) Gene Family in Melanoma

Mon, 04 Feb 2013 20:00:00 GMT
Using exon capture and next generation sequencing approaches to analyze the entire G protein coupled receptor (GPCR) gene family in melanoma, the researchers at the NIH have identified several novel somatic (e.g., tumor-specific) alterations. GPCRs play an integral part in regulating physiological functions and the importance of these molecules is evident by the fact that approximately half of the current FDA approved therapeutics target GPCRs or their direct downstream signaling components.

Many of the GPCR gene mutations identified by the NIH researchers were mutated in a large portion of melanoma patients and already have inhibitors, the most notable being the Glutamate Receptor Metabotropic 3 (GRM3) mutation which could be functionally signification for melanoma tumorigenesis. Therefore, this technology could aid in the development of specific inhibitors of GRM3 as well as the pathway it activates, mitogen-activated protein kinase (MEK), for the treatment of melanoma patients with these mutations. To complement these findings, human melanoma metastatic cell lines harboring GRM3 mutations are also available for licensing. CRADA Opportunity: The NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Claire Driscoll, Director, NHGRI Technology Transfer Office, at cdriscol@mail.nih.gov or 301-594-2235.

Single Domain Human Monoclonal Antibodies To Mesothelin for Treatment of Cancer

Fri, 25 Jan 2013 01:00:00 GMT
Mesothelin is a cell surface protein that is highly expressed in aggressive cancers such as malignant mesothelioma, ovarian cancer and pancreatic cancer. This selective expression makes mesothelin an excellent candidate for targeted therapeutics such as monoclonal antibodies (mAbs) and corresponding chimeric molecules. Unfortunately, current anti-mesothelin mAb candidates have drawbacks, such as competition with a serum protein (MUC16/CA125) for binding to mesothelin, the formation of neutralizing antibodies because they are non-human antibodies, and the inability to trigger complement-dependent cytotoxicity (CDC).

In order to address this concern, NIH inventors generated two single domain human mAbs: SD1 and SD2. SD1 recognizes a unique epitope in region III of mesothelin which is not out-competed for binding by MUC16/CA125. SD1 was also capable of triggering CDC, as well as antibody-dependent cellular cytotoxicity (ADCC). Due to its human origin, SD1 is also less likely to elicit the formation of neutralizing antibodies when administered to patients. Each of these characteristics suggests SD1 may be an effective therapeutic agent. Indeed, SD1 was able to inhibit tumor growth in mouse xenograft models, and corresponding immunotoxins were able to inhibit tumor cell growth in vitro, supporting the use of SD1 as a therapeutic mAb. CRADA Opportunity: The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize single-domain human antibodies (SD1 and SD2) to mesothelin for cancer therapy or diagnostics. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

High-Affinity Rabbit Monoclonal Antibodies To Mesothelin for Treatment of Cancer

Thu, 24 Jan 2013 06:00:00 GMT
Mesothelin is a cell surface protein that is highly expressed in aggressive cancers, such as malignant mesothelioma, ovarian cancer and pancreatic cancer. Because of this selective expression, mesothelin is an excellent candidate for targeted therapeutics, such as monoclonal antibodies (mAbs) and chimeric molecules. Current anti-mesothelin therapeutic mAb candidates bind to an epitope in Region I of mesothelin. Unfortunately, Region I contains the interaction site MUC16/CA125, a mesothelin-interacting protein that is present in the serum of patients with mesothelin-related cancers. Because the current therapeutic mAb candidates must compete with MUC16/CA125 for binding to mesothelin, they may not reach their full therapeutic potential due to interference.

In order to address this concern, NIH inventors generated several rabbit mAbs that recognize unique epitopes of mesothelin: (1) YP223, which recognizes region II; (2) YYP218, which recognizes region III; and (3) YP3 which recognizes a native conformation epitope of mesothelin. These mAbs bind to mesothelin with sub-nanomolar affinity and are not out-competed for binding by the current anti-mesothelin therapeutic mAb candidates or MUC16/CA125. This strong binding affinity for an alternative binding site on mesothelin suggests that these mAbs are excellent therapeutic candidates. CRADA Opportunity: The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize new monoclonal antibodies to unique domains of mesothelin for cancer therapy or diagnostics. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Novel Derivatives of Docosahexaenoylethanolamide as Therapeutics for Neuronal Disorders

Thu, 24 Jan 2013 11:00:00 GMT
This technology provides derivatives of Docosahexaenoylethanolamide (synaptamide or DEA) which have increased potency and hydrolysis resistance as compared to DEA (structures of these derivatives are available upon request), as well as methods of using these derivatives to promote neurogenesis, neurite growth, and/or synaptogenesis. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid that accumulates in the brain during development, has been shown to play a key role in learning and memory development. Studies have also shown that DEA, a metabolite derived from DHA is very potent in accelerating neuronal growth and development. The inventors have discovered that the novel DEA derivatives they have designed are even more potent than DEA or DHA in accelerating neuronal growth, synaptogenesis and development. The inventors have shown that treatment of progenitor neural cells with some of these novel DEA derivatives leads to an increase in the amount of somatic neurons produced after differentiation. These novel compounds can be developed as therapeutics for conditions such as trauma, stroke, multiple sclerosis, Alzheimer's disease, brain and spinal cord injuries, and peripheral nerve injuries for rehabilitation. CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Dr. Juan Marugan at maruganj@mail.nih.gov or Dr. Krishna Balakrishnan at balakrik@mail.nih.gov.

Multivalent Meningiococcal Conjugates and Methods for Preparing Conjugates

Wed, 23 Jan 2013 16:00:00 GMT
Among 13 isolated meningococcal serogroups, A, B, C, W-135 and Y are the most prevalent. There are three FDA-approved capsular polysaccharide (PS)-based vaccines, one tetravalent PS vaccine, and two tetravalent conjugate vaccines for protection against meningococcal disease caused by groups A, C, W-135 and Y Neisseria meningitidis. Group B capsular PS is similar to the PS structure expressed in certain human tissues, thus making it a poor immunogen. Furthermore, if used as a vaccine, the possibility exists of it inducing an autoimmune response. Thus, a need remains to develop additional meningococcal vaccines, particularly for group B and group X meningococcal serogroups.

This application claims immunogenic conjugates including at least one polysaccharide conjugated to a group B factor H binding protein (fHbp). Also claimed are immunogenic conjugates including at least one polysaccharide conjugated to a Neisserial surface protein A (NspA). Additionally, improved methods for preparing conjugates are claimed. CRADA Opportunity: The FDA/CBER is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Multivalent Meningiococcal Conjugates and Methods for Preparing Conjugates. For collaboration opportunities, please contact Che-Hung Robert Lee at robert.lee@fda.hhs.gov or 301-451-5934.

SIRT2 Inhibitors as Novel Therapeutics for Myocardial Infarction and Ischemic Stroke and to Prevent Necrosis

Wed, 23 Jan 2013 21:00:00 GMT
Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. These investigators also found that genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha and RIP1 is a critical target of SIRT2-dependent deacetylation. Further studies also showed that the hearts of Sirt2^–/– mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischemic injury. These results implicate SIRT2 as an important regulator of programmed necrosis and indicate that SIRT2 inhibitors may constitute a novel approach to protect against necrotic injuries, including ischemic stroke and myocardial infarction. CRADA Opportunity: The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize retinoid-related orphan receptors (RORs) function in chronic diseases. For collaboration opportunities, please contact Ms. Peg Koelble at koelblep@mail.nih.gov or 301-594-4095.

Virus-Like Particles Mediated Protein and RNA Delivery

Sat, 12 Jan 2013 02:00:00 GMT
The invention is directed to novel virus-like particles (VLPs) that are capable of binding to and replicating within a target mammalian cell, including human cells. The claimed VLPs are safer than viral delivery because they are incapable of re-infecting target cells. The present VLPs can optionally comprise inhibitory recombinant polynucleotides, such as microRNA, antisense RNA or small hairpin RNA, to down regulate or turn off expression of a particular gene within the target cell. Alternatively, recombinant polynucleotides packaged within VLPs can comprise a gene encoding a therapeutic protein so as to enable expression of that protein within the target cell. Specifically, VLPs of the invention are composed of an alphavirus replicon that contains a recombinant polynucleotide, a retroviral gag protein, and a fusogenic envelope glycoprotein.

While the claimed VLPs have a variety of applications, therapeutic uses of the VLPs include directing antibody synthesis and converting cancer cells into antigen presenting cells. Additional applications include using VLPs to induce fast (approx. 3-4 hrs) and high levels of protein production in mammalian cells. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Novel Delivery of Packaged RNA to Mammalian Cells. For collaboration opportunities, please contact Kevin Brand at brandk@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Small, Stable, Functional, Soluble, Monomeric IgG1 Fc Molecules Engineered Therapies

Fri, 11 Jan 2013 07:00:00 GMT
This technology relates to small (~27 kDa) antibody fragments that are potentially useful for therapeutic development. These are monomeric IgG fragment crystalizable (mFc) compositions; they are long half-lived, functional (pH dependent binders of neonatal Fc receptor - FcRn); and they are soluble and express efficiently in E. coli. These molecules may serve as a platform for development of engineered mFc-based antibodies and fusion proteins with therapeutic applications. Efforts to engineer antibody-based therapeutics, to date, have encountered technical limitations due to the relatively large fragment size and short fragment half-life. The IgG fragment crystalizable (Fc) is a dimer of two constant domains (CH2-CH3 chains). Fc has a long half-life, which makes it promising as a candidate for engineering antibody therapeutics. Fusion proteins based on Fc dimer molecules demonstrate extended half-life, due to the ability to bind FcRn at acidic pH. However, the relatively large size of the Fc domains (~50 kD) is not optimal. This technology uses smaller (~27 kDa) mFc compositions that retain efficient binding to human FcRn and demonstrate long half-life. These mFc compositions are promising for the development of novel therapeutics because the smaller size may allow for superior access to targets and tissues compared to full sized mAbs and larger fragment-based therapeutics, while also retaining important function characteristics. CRADA Opportunity: The NCI/CCR/NP is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Small, Stable, Functional, Soluble, Monomeric IgG1 Fc Molecules Engineered Therapies. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Simple Direct Zirconium-89 Cell PET Label, 89Zr-Labeled Cells, and Methods for Real-time In Vivo Pet Imaging

Fri, 11 Jan 2013 12:00:00 GMT
The capability to image cells and cellular processes in real time over a scale of days could dramatically improve research insights and the effectiveness of cell-based therapies. Zirconium-89 (⁸⁹Zr) has a half-life of over three days (78.4 hours) over 44 times longer compared to Fluorine (¹⁸F) the most commonly used PET isotope (half-life of 1 hour and 50 minutes). ⁸⁹Zr is also advantageous compared to other long half-life isotopes because it is not limited by high background activity and cell toxicity. Labeling cells with ⁸⁹Zr, is currently accomplished by indirect methods using secondary cell-type specific reagents such as antibodies. This technology is a PET imaging complex of ⁸⁹Zr and polycation that is internalized by the cells. This complex has been able to directly label a wide range of cells, without the use of secondary reagents. ⁸⁹Zr-labeled cells of lymphocytic lineage, including T cells, natural killer T-cells, macrophages, dendritic cells, and stem cells, have been produced and imaged in vivo with minimal damage to the cells. This PET imaging agent can be readily combined with an MR imaging agent for combined PET/MR imaging of cells. The imaging capabilities enabled by this technology may significantly improve cell therapies, cell level diagnostics and aid research for non-cell based therapies. CRADA Opportunity: The NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Optical Microscope Software for Breast Cancer Diagnosis

Fri, 11 Jan 2013 17:00:00 GMT
The instant invention discloses a software to analyze optical microscopic images of human breast tissue sections for diagnosing cancer by using the differences in spatial positioning of certain genes. The software uses the inherent hierarchy in the data and stores all the analysis and manual interaction information in a highly structured XML file. It is a user-friendly software to discriminate normal and cancerous human breast tissue section images that can be used for large experiments. Additionally the software uses a cluster of computers in the background to reduce the analysis time for large image datasets. Furthermore, the software of instant invention provides a set of tools for performing diagnostic or prognostic assays on new unseen datasets. CRADA Opportunity: The SAIC-Frederick Optical Microscopy and Analysis Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Typhoid-Plague Bivalent Vaccine

Fri, 11 Jan 2013 22:00:00 GMT
Yersinia pestis (Y. pestis) bacteria is the causative agent of plague, typically transmitted from animals to humans by the bite of an infected flea. Y. pestis infection of the lungs leads to pneumonic plague, which is highly contagious and generally fatal. Y. pestis is a potential bioterrorist threat agent for which no vaccine yet exists.

This invention claims the generation and development of a candidate oral vaccine against plague. The vaccine consists of a synthetic gene construct that expresses a Y. pestis F1-V fusion antigen linked to a secretion signal, resulting in the production of large amounts of the F1-V antigen. The F1-V synthetic gene fusion is housed within Ty21a, an attenuated typhoid fever strain that is licensed for human use as a live oral bacterial vaccine. Ty21a serves as a carrier to deliver the F1-V fusion antigens of the plague bacteria; the combined F1-V fusion in the Ty21a carrier has been shown to stimulate a robust immune response in mice. The possibility of combining the oral plague vaccine of this invention with FDA’s candidate oral anthrax vaccine exists and would result in an easy-to-administer oral delivery system to streamline administration of the vaccine to large numbers of recipients in emergency situations. CRADA Opportunity: The FDA Center for Biologics Evaluation and Research, Lab of Enteric and Sexually Transmitted Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize oral plague vaccine. For collaboration opportunities, please contact Dennis Kopecko at dennis.kopecko@fda.hhs.gov.

Cross-Reactive Dengue Fully Human Monoclonal Antibodies

Sat, 12 Jan 2013 03:00:00 GMT
Among the arthropod-borne flaviviruses, the four dengue virus serotypes, dengue type 1 virus (DENV-1), dengue type 2 virus (DENV-2), dengue type 3 virus (DENV-3), and dengue type 4 virus (DENV-4) are most important in terms of human morbidity and geographic distribution. Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitoes are abundant.

A safe and effective vaccine against dengue is currently not available. Passive immunization with monoclonal antibodies from non-human primates or humans represents a possible alternative to vaccines for prevention of illness caused by dengue virus. This invention claims fully human monoclonal antibodies that bind and neutralize dengue type 1, 2, 3 and 4 viruses. It also claims fragments of such antibodies and nucleic acids encoding the antibodies of the invention as well as prophylactic, therapeutic and diagnostic methods employing the antibodies and nucleic acids of the invention. CRADA Opportunity: The NCI/CCR/NP is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Cross-Reactive Dengue Fully Human Monoclonal A. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Methods and Composition for Identification of Variants of JC Virus DNA; An Etiologic Agent for Progressive Multifocal Leukoencephalopathy (PML)

Fri, 11 Jan 2013 08:00:00 GMT
JC Virus causes a fatal disease in the brain called progressive multifocal leukoencephalopathy (PML) that occurs in many patients with immunocompromised conditions. The finding of JCV DNA in the patients with neurological symptoms of PML is a diagnostic criterion and is needed to confirm the diagnosis of PML to rule out other neurological conditions. Certain JC virus variants are known to have a greater association with PML. For example, "Prototype" JC virus is far more pathogenic than "Archetype" JC virus.

This invention claims novel assays for identifying Archetype and/or Prototype JC virus by detecting the presence or absence of the unique Archetype nucleic acid sequence in the non-coding regulatory region of JC virus. While the sequences of Archetype and Prototype JC virus are known, these are the first assays that allow discrimination between Prototype and Archetype JC virus in a simple assay without the need for DNA sequencing. The identification of a JC virus as a prototype can lead to early treatment of infected individuals. CRADA Opportunity: The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize assays for the detection of JC Virus. For collaboration opportunities, please contact Melissa Maderia at maderiam@mail.nih.gov or 301-451-3943.

Transmission-Blocking Malaria Vaccine

Fri, 11 Jan 2013 13:00:00 GMT
There is no vaccine for malaria, and there is growing resistance to existing anti-malarial drugs. Sexual stage-specific antigens are of interest as vaccine candidates because disruption of these antigens would reduce the fertility and, thus, the infectivity of the parasite.

This invention claims methods and compositions for delivering a Plasmodium P47 vaccine or antibody to P47 to prevent Plasmodium falciparum or Plasmodium vivax malaria. P47 and other antigens have been mentioned as potential transmission-blocking vaccines due to their surface location on gametes. The gene for P47 antigens is also well characterized. Recent discoveries have noted that P47 allows the parasite to suppress or evade the immune system, thereby ensuring the mosquitoes' survival. Recent discoveries have also shown the mechanism by which P47 enables survival of the parasite by manipulation of the mosquito immune system. Based on the critical role of P47 antigens in transmission, the disruption of the function of P47 by various means can be an innovative and forceful means to control and/or reduce the prevalence of malaria. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases (NIAID) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize malaria vaccines, diagnostics and therapeutics. For collaboration opportunities, please contact Tristan J. Mahyera at tristan.mahyera@nih.gov or 301-827-0251.

Nitric Oxide-Releasing Polyvinylpyrrolidone-Based Polymers for Wound Healing and Related Applications

Mon, 26 Nov 2012 18:00:00 GMT
Novel nitric oxide-releasing polyvinylpyrrolidone-based polymers, their compositions, and use in treating wounds. The disclosed polymers appear to be stable, biocompatible and bioabsorbable, while providing for extended nitric oxide release at therapeutic levels. The invention also encompasses medical devices, such as wound dressings and bandages, which include the polymers and are capable of releasing nitric oxide when in use. These devices may be used to treat a wound, various infections, and dermatological conditions.

The therapeutic efficacy of nitric oxide has been demonstrated for many indications, including wound healing. As wounds are deficient in nitric oxide, its application has been shown to have beneficial effects on wound healing by promoting angiogenesis and tissue remodeling. CRADA Opportunity: The National Cancer Institute Chemical Biology Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize NO-releasing polymers for applications in wound healing. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Diagnostic Test and Therapeutic Target for Sjogren's Syndrome

Wed, 21 Nov 2012 23:00:00 GMT
Sjögren's syndrome is an autoimmune disease that attacks salivary glands resulting in chronic dry mouth and dry eyes. Currently, there is no single diagnostic test to confirm the presence of Sjögren's. Physicians presently reach diagnosis after conducting a series of blood and functional tests for tear and salivary production. Diagnosis is further complicated as Sjögren's symptoms frequently mimic those of other autoimmune diseases (e.g., lupus, rheumatoid arthritis, etc.) and is often overlooked as dryness associated with medications being taken by the patient.

Researchers at NIDCR have identified overexpression of a growth factor, bone morphogenetic protein 6 (BMP6), in patients with Sjögren's. By detecting BMP6 expression and/or activity, this invention potentially presents a singular confirmation to diagnose those suffering and those at risk for developing Sjögren's. BMP6 also presents a potential therapeutic target for Sjögren's, a disease for which there is presently no cure.

Researchers have also discovered unique expression profiles for two other genes (XIST and MECP2) in male Sjögren's patients. Detecting aberrant expression and/or activity of these genes also offer a potential singular test for diagnosing Sjögren's in male subjects. CRADA Opportunity: The NIDCR is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize BMP6 Based Diagnosis and Treatment of Sjögren's. For collaboration opportunities, please contact David W. Bradley, Ph.D. at bradleyda@nidcr.nih.gov.

Axon Regeneration After Brain or Spinal Cord Injury

Thu, 22 Nov 2012 04:00:00 GMT
The invention is directed to modification of a particular sugar by the enzyme arylsulfatase B (ARSB), which results in axon regeneration.

Following traumatic brain or spinal cord injury, glial scars prevent regeneration of axons. Chondroitin sulfate proteoglycans (CSPGs) are major components of glial scars. CSPGs are made of a protein core containing glycosaminoglycan (GAG) sugar side chains, which, when sulfated, are responsible for the inhibitory activity of glial scars. Specifically, NIH researchers have shown that the 4-sulfate unit on a certain sugar on GAG is responsible for inhibiting axon regrowth and, when the 4-sulfate unit is reduced, axon regrowth is observed. Moreover, removal of this 4-sulfate unit by the ARSB enzyme promotes axon regrowth.

As a potential therapy for spinal cord injuries, researchers developed a vector expressing ARSB and demonstrated that this vector promotes axon regeneration when injected into the spinal cord of a mouse. CRADA Opportunity: The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of ARSB in axonal regeneration after brain or spinal cord injury using animal models. For collaboration opportunities, please contact Denise Crooks, Ph.D. at 301-435-0103 or crooksd@mail.nih.gov.

Small Molecule MRS5474 with Anticonvulsant Activity for Treatment of Epilepsy

Fri, 16 Nov 2012 09:00:00 GMT
Adenosine modulates many physiological processes by activating specific adenosine receptors. These adenosine receptors play a critical role in the regulation of cellular signaling and are broadly distributed throughout the body. Thus, the ability to modulate adenosine receptor-mediated signaling is an attractive therapeutic strategy for a broad range of diseases. This technology relates to a group of compounds that display high affinity and specificity for the A1 adenosine receptor subtype.

One of the compounds, MRS5474, displays anticonvulsant activity in the 6 Hz animal model of clonic seizures. In the minimal behavioral toxicity test using the rotarod, no toxicity (zero out of eight mice) was observed at all doses tested up to 30 mg/kg, the highest dose tested, which was nearly completely protective (seven out of eight animals) in the 6 Hz model. MRS 5474 also tested well in the corneal kindled mouse model to examine its effect on focal seizures. CRADA Opportunity: The NIDDK is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MRS5474, A1 adenosine receptor agonist for treatment of seizures. For collaboration opportunities, please contact Marguerite Miller at millermarg@mail.nih.gov.

Adeno-Associated Virus Gene Therapy for Diabetes and Obesity

Fri, 16 Nov 2012 14:00:00 GMT
This invention is directed to adeno-associated virus (AAV) vector delivery of exendin-4 (Ex-4) to salivary glands as treatment for diabetes and obesity. Ex-4 is a potent and long-acting agonist of the receptor for glucagon-like peptide 1 (GLP-1). Scientists at NIDCR have shown that AAV-mediated delivery of Ex-4 resulted in improved glucose homeostasis and weight profile in two rat models of obesity and type 2 diabetes. Further, AAV-mediated delivery of Ex-4 to rat salivary glands resulted in localized and sustained expression of Ex-4 that was biologically active and well tolerated.

AAV-mediated delivery of Ex-4 is superior to administering GLP-1 analogs in that AAV-Ex-4 expression is more stable and longer acting. Like GLP-1 analogs, Ex-4 expression also potentially provides beneficial effects like reduced hypoglycemia, appetite suppression, and potential weight loss. CRADA Opportunity: The NIDCR is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize treatment of diabetes by expression NGF-extendin 4 protein. For collaboration opportunities, please contact David Bradley, Ph.D. at 301-402-9242 or bradleyda@nidcr.nih.gov.

Novel Small Molecule Agonists of the Relaxin Receptor as Potential Therapy for Heart Failure and Fibrosis

Fri, 16 Nov 2012 19:00:00 GMT
The present invention is directed to novel small molecule agonists of the mammalian relaxin family receptor 1 (RXFP1), including human RXFP1. Activation of RXFP1 induces: 1) vasodilation due to up-regulation of the endothelin system; 2) extracellular matrix remodeling; 3) moderation of inflammation by reducing levels of inflammatory cytokines; and 4) angiogenesis. Small molecule agonists of RXFP1 may be useful in treating acute heart failure (AHF), scleroderma, fibrosis, other conditions associated with the biology of relaxin, and in improving reproductive health and wound healing. These compounds are the first and only small molecule agonists of RXFP1. CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize small molecule agonists of RXFP1. For collaboration opportunities, please contact Krishna (Balki) Balakrishnan, Ph.D. at 301-217-2336 or balki@nih.gov. A Collaborative Research/Licensing Opportunity Notice related to this technology was published in the Federal Register on Wednesday, February 6, 2013 (78 FR 8544); this notice may be viewed at http://www.gpo.gov/fdsys/pkg/FR-2013-02-06/pdf/2013-02611.pdf.

Activation of Therapeutic Functionalities with Chimeric RNA/DNA Nanoparticles for Treatment of Cancer, Viruses and Other Diseases

Wed, 07 Nov 2012 00:00:00 GMT
A new strategy based on RNA/DNA hybrid nanoparticles, which can be generally used for triggering multiple functionalities inside diseased cells is presented. Individually, each of the hybrids is functionally inactive and functional representation can only be activated by the re-association of at least two cognate hybrids simultaneously present in the same cell. Overall, this novel approach allows (i) the triggered release of therapeutic siRNAs or miRNAs inside the diseased cells, (ii) activation of other split functionalities (e.g. FRET, different aptamers, rybozymes, split proteins) intracellularly, (iii) higher control over targeting specificity (e.g. if two hybrids are decorated with two different tissue specific recognition moieties), (iv) biosensing and tracking of the delivery and re-association of these hybrids in real-time inside cells, (v) increasing the number of functionalities by introducing a branched hybrid structure, (vi) introduction of additional functionalities without direct interference of siRNA processivity, (vii) increasing the retention time in biological fluids by fine-tuning chemical stability through substituting the DNA strands with chemical analogs (e.g. LNA, PNA, etc.), (viii) conditional release of all functionalities. CRADA Opportunity: The NCI Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize therapeutic RNA/DNA nanoparticles. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Selective Treatment of Cancer, HIV, Other RNA Viruses and Genetically Related Diseases Using Therapeutic RNA Switches

Tue, 06 Nov 2012 05:00:00 GMT

Targeted therapy in cancer or viral infections is a challenge because the disease state manifests itself mainly through differences in the cell interior, for example in the form of the presence of a certain RNAs or proteins in the cytoplasm.

The technology consists of designed RNA switches that activate the RNA interference pathway only in the presence of a trigger RNA or DNA to which they bind, in order to knock down a chosen gene that is not necessarily related to the initial trigger.

This new approach can lead to a new type of drug that has the unique feature of selectively causing a biochemical effect (such as apoptosis) in cells that are infected by RNA viruses (such as HIV), as well as cancer cells. The RNA switch concept can be expanded to selectively treat other genetically related diseases.
CRADA Opportunity: The NCI Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize therapeutic RNA switches. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Cyclodextrins as Therapeutics for Lysosomal Storage Disorders

Tue, 06 Nov 2012 10:00:00 GMT

Cyclodextrins (CD), alone or in combination with other agents (e.g., vitamin E), as therapeutics for the treatment of lysosomal storage disorders (LSDs) caused by the accumulation of non-cholesterol lipids.

CDs are sugar molecules in a ring form. The alpha-CD (6 sugars), beta-CD (7 sugars) and gamma-CD (8 sugars) are commonly used cyclodextrins. The hydroxypropyl-beta cyclodextrin (HPbCD) has been approved for pharmaceutical use. Recent reports show that beta-cyclodextrin including HPbCD and beta-methyl-cyclodextrin reduced cholesterol accumulation and neuronal cell loss in the mouse model of NPC1 disease.

NCATS investigators found that CD (alpha-, beta- and gamma-CDs) increased intracellular Ca2+ and lysosomal exocytosis in both wild type cells and cells with Wolman disease, and reduced the size of enlarged lysosomes in six patient cell lines with LSDs. Further, CD in combination with tocopherol synergistically/additively reduced cholesterol accumulation in cells of NPC and Wolman diseases. Based on these results, they propose treatment of LSDs with cyclodextrins (such as alpha and gamma forms) alone or in combination with Vitamin E and its analogues for better efficacy and less side effects.
CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Dr. Juan Marugan at maruganj@mail.nih.gov.

Glucocerebrosidase Activators for the Treatment of Gaucher Disease, Parkinson's Disease, and Other Proteinopathies

Tue, 06 Nov 2012 15:00:00 GMT

Gaucher disease is a rare lysosomal storage disease that is characterized by a loss of function of the glucocerebrosidase (GCase) enzyme, which results in a decreased ability to degrade its lipid substrate, glucocerebroside. The intracellular build up of this lipid causes a broad range of clinical manifestations, ranging from enlarged spleen/liver and anemia to neurodegeneration. In Gaucher disease, the loss of GCase function has been attributed to low levels of the protein in the lysosomal compartment, resulting from improper GCase folding and transport. Also, mutations in the GCase gene have been linked to some forms of Parkinson's disease, and may also be involved in other proteinopathies.

This technology describes a collection of salicylic acid-derived small molecules that act as chaperones to activate proper GCase folding and subsequent transport from the endoplasmic reticulum into the lysosome. Unlike many other small molecule chaperones, these salicylic acid derivatives do not inhibit the activity of the GCase enzyme. These small molecules have been tested for the ability to activate GCase in vitro and show chaperone activity in a patient-derived fibroblast translocation assay.
CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Dr. Juan Marugan at maruganj@mail.nih.gov. A Collaborative Research/Licensing Opportunity Notice related to this technology was published in the Federal Register on Wednesday, February 6, 2013 (78 FR 8546); this notice may be viewed at http://www.gpo.gov/fdsys/pkg/FR-2013-02-06/pdf/2013-02609.pdf.

Improved Monoclonal Antibodies Against Neuregulin 2

Tue, 06 Nov 2012 20:00:00 GMT
The invention provides highly selective monoclonal antibodies against the extracellular domain (ECD) or intracellular domain (ICD) of neuregulin-2, a ligand for the ErbB receptors in adult human brain. Neuregulins regulate a diverse array of neurological process in the central nervous system and are implicated in schizophrenia and other psychiatric disorders. However, an understanding of the specific role of neuregulin 2 has been hindered by a lack of specific antibodies useful in immunoblotting and immunohistology studies. Commercially available antibodies do not perform as well in these applications when compared to the invention antibodies. A mouse monoclonal antibody directed to the ECD is available for licensing (clone 8D11, HHS Ref. No. E-192-2012), and rabbit antibodies directed to the ICD are also available (clone 11-11, HHS Ref. No. E-193-2012; clone 15-10, HHS Ref. No. E-189-2012; and clone 9-2, HHS Ref. No. E-188-2012). Antibodies from clones 8D11 and 11-11 have been validated for immunohistology and antibodies from clones 15-10 and 9-2 have been validated for Western blotting using brain tissue from wild-type and neuregulin 2 deficient mice. CRADA Opportunity: The NICHD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize neuregulin-2 monoclonal antibodies. For collaboration opportunities, please contact Charlotte McGuinness at mcguinnc@mail.nih.gov.

Cell Lines Expressing Nuclear and/or Mitochondrial RNase H1

Wed, 07 Nov 2012 01:00:00 GMT
RNase H1 has been shown to remove RNA/DNA hybrids and either too much or too little enzyme can lead to undesirable effects such as deletions of DNA. The gene encoding RNase H1 in mammalian cells produces two forms of the protein. One is targeted to the nucleus of the cell and the other to the mitochondrial organelle. To study the effects of expression as well as to understand the regulation of the frequency with which each form is made, NIH investigators constructed cells derived from HEK293 cells where expression of each or both forms is/are expressed only after addition of doxycycline as a small molecule inducer compound. The set of cell lines could be important in the process of analysis of RNA/DNA hybrids as each cell line expresses different amounts of each form. CRADA Opportunity: The Program in Genomics of Differentiation, NICHD, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize small molecule inhibitors of RNase H1, genome instability, or transcription and translation. For collaboration opportunities, please contact Joseph Conrad III, Ph.D. at jmconrad@mail.nih.gov. Click here to view the NICHD collaborative opportunity announcement.

Antimalarial Inhibitors that Target the Plasmodial Surface Anion Channel (PSAC) Protein and Development of the PSAC Protein as Vaccine Targets

Mon, 22 Oct 2012 05:00:00 GMT
There are two related technologies, the first being small molecule inhibitors of the malarial plasmodial surface anion channel (PSAC) and the second being the PSAC protein itself as a vaccine candidate. The PSAC protein is produced by the malaria parasite within host erythrocytes and is crucial for mediating nutrient uptake. In vitro data show that the PSAC inhibitors are able to inhibit growth of malaria parasites, have high specificity, and low toxicity. Portions of the PSAC protein are found on the outer surface of infected host erythrocytes and the protein was recently shown to be encoded by the clag3 gene. This discovery opens the possibility of developing the PSAC protein as a potential vaccine candidate against malaria. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Antimalarial Inhibitors that Target the Plasmodial Surface Anion Channel (PSAC) Protein. For collaboration opportunities, please contact Dana Hsu at dhsu@niaid.nih.gov or 301-451-3521.

Topical Antibiotic with Immune Stimulating Oligodeoxynucleotide Molecules to Speed Wound Healing

Mon, 22 Oct 2012 09:00:00 GMT
The present technology provides a mean of improving the activity of topical antibiotics. Currently available topical antibiotic formulations effectively eliminate bacteria at a wound site. But in eliminating bacteria in the wound, such antibiotics also eliminate the molecular signals present in bacterial DNA that stimulate to immune system's wound healing processes. Without these signals the rate of wound healing is diminished. It would be desirable for topical antibiotics to remove infectious bacteria but also provide the immune stimulating signals needed to promote and accelerate healing. The present formulation accomplishes these goals by supplementing the antibiotic formulation with immunostimulatory oligodeoxynucleotides (ODN). These ODN express the CpG motifs present in bacterial DNA and safely mimic the immune stimulation induced by bacterial DNA. The formulation may be applied directly to a wide variety of wounds to skin (such as traumatic, burn, or surgical wound), or the eyes (such as corneal abrasions) to effectively eliminate infection and stimulate rapid healing of the wound. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize adding immunostimulatory CpG oligonucleotides to a topical antibiotic formulation to accelerate wound healing. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Magnetic Resonance Arterial Wall Imaging Methods that Compensate for Patient Aperiodic Intrinsic Cardiac, Chest Wall, and Blood Flow-Induced Motions

Mon, 22 Oct 2012 13:00:00 GMT

The technology includes MRI methods, systems, and software for reliably imaging vasculature and vascular wall thickness while compensating for aperiodic intrinsic motion of a patient during respiration. To overcome the loss of the orthogonality due to uncompensated residual motions and after a lapse of time equal to the trigger delay commenced at the cardiac cycle, the system acquires multiple consecutive time-resolved images of the arterial wall. The cine images are processed offline and a wall thickness measurement is produced.

The method improves arterial wall imaging by increasing the success rate of obtaining good and excellent quality images and imaging slice-vessel orthogonality. The method also provides more precise wall measurements and a more distinct difference between healthy subjects and patients.

The methodology and system can be applied to any commercially available MRI scanner.
CRADA Opportunity: The Biomedical and Metabolic Imaging Branch, NIDDK, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize time-resolved arterial wall imaging. For collaboration opportunities, please contact Khaled Z. Abd-Elmoniem at abdelmoniemkz@mail.nih.gov.

Zuma Mutant Mice as a Tool for Investigating Mammalian Developmental Defects

Mon, 22 Oct 2012 17:00:00 GMT

In vertebrates, mutations in different ribosomal protein subunits result in a variety of phenotypes, suggesting unique and perhaps extra-ribosomal functions for these proteins. Diamond-Blackfan Anemia (DBA) is a ribosomal protein disease, in which the bone marrow fails to produce red blood cells.

NHGRI investigators recently generated a mouse line with a mutation in small ribosomal protein7 (Rps7), known to be involved in DBA. This line named Zuma (made with the use of the mutagen N-ethyl-N-nitrosourea (ENU)) carries a point mutation in exon 7 of Rps7, which is predicted to cause a substitution of a conserved amino acid (pY177S). The mutation results in the disruption of ribosomal biogenesis, as well as in abnormal skeletal, melanocyte, and central nervous system development. Thus, the Zuma line can be used as a model of DBA, as well as a tool for investigating other defects of mammalian development.
CRADA Opportunity: The Mouse Embryology Section of the National Human Genome Research Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Diamond-Blackfan Anemia therapies. For collaboration opportunities, please contact Claire T. Driscoll, Director, NHGRI Technology Transfer Office, at cdriscoll@mail.nih.gov or 301-594-2235.

Human Antibodies and Fusion Proteins with Potent and Broad HIV-1 Neutralizing Activity

Fri, 28 Sep 2012 21:00:00 GMT
The inventions listed below provide multiple novel human anti-HIV-1 domain antibodies (m36 and its affinity- matured versions) and their fusion proteins with two-domain or single-domain human soluble CD4 (sCD4) that can potentially be used alone or synergistically with other anti-HIV-1 antibodies and antiretroviral drugs as therapeutics and/or preventatives for infection by different HIV-1 strains.

Some of the inventions listed below also describe some fusion proteins as vaccine immunogens that could elicit broadly neutralizing antibodies against HIV-isolates from different clades. One invention also describes the methods to prepare and use the immunogens in the vaccination for prevention of HIV-1 infections. More specifically, the later invention provides a vaccine composed of a primary immunogen and a secondary immunogen, and a method for making the vaccine which could be effective in eliciting desired broadly neutralizing antibodies. The primary immunogen could be effective in activating B cell receptors (BCRs) that are on the maturational pathways of the desired antibodies and have an intermediate degree of somatic mutational diversity. The secondary immunogen contains epitopes of the desired antibodies and could be effective in further diversifying the BCRs sufficiently to form mature BCRs that have the identical or substantially identical sequence as the desired antibodies. CRADA Opportunity: The NCI CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize m36, single domain sCD4, and related fusion proteins as candidate therapeutics against HIV-1. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Modulation of Regulatory T-Cell and B-Cell Lymphocytes for the Treatment of Autoimmune and Other Disease Indications

Sat, 29 Sep 2012 01:00:00 GMT
A method of modulating the immune response by affecting the activity of the regulatory lymphocytes through targeting of the Hepatitis A Virus receptor 1 (HAVCR1) receptor. This methodology can be developed for the treatment of autoimmune diseases, allergies, prevention of transplant rejection, and incorporated into therapeutic strategies for cancer.

Regulatory lymphocytes, such as regulatory T-cells (Tregs) and B-cells (Bregs), play a significant role in suppressing and controlling immune responses to antigens, including allergens and self-antigens that induce autoimmune diseases. The Tregs and Bregs also control the immune responses to microbial pathogens thereby limiting excessive damage to tissue. HAVCR1 is expressed on these regulatory lymphocytes and functions as a master regulator of these cells. CRADA Opportunity: The Center for Biologics Evaluation and Research, Laboratory of Emerging Pathogens, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize targeting of HAVCR1 to control Treg and Breg function in human diseases. For collaboration opportunities, please contact Gerardo Kaplan at gerardo.kaplan@fda.hhs.gov.

A Novel Immortalized Human Adrenal Cell Line with Inactive Protein Kinase A for Studies on cAMP Signaling and Endocrine Tumorigenesis

Fri, 28 Sep 2012 05:00:00 GMT
The first known immortalized cell line with a naturally-occurring inactivating mutation in PRKAR1A, the regulatory subunit type 1A (R1alpha) of protein kinase A (PKA), which is associated with tumor formation.

PKA isozyme balance is critical for the control of cAMP signaling and related cell cycle and proliferation changes. Aberrant cAMP signaling has been linked to adrenocortical and other, mostly endocrine, tumors. Inactivating mutations in the PRKAR1A gene are a known cause of Carney Complex - an autosomal dominant multiple neoplasia syndrome associated with skin, heart, and other myxomas and a variety of endocrine tumors. CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Joseph Conrad III, Ph.D. at jmconrad@mail.nih.gov. Click here to view the NICHD collaborative opportunity announcement.

Use of Erythropoietin and Derivatives for Treatment of Hypertension

Tue, 11 Sep 2012 09:00:00 GMT
Erythropoietin (EPO), a natural hormone produced by kidneys, is associated with stimulation of red blood cell production. Recombinant human erythropoietin (rhEPO) is currently used for treatment of anemia and has powerful cardioprotective properties. Hypertension remains a major health problem and a serious risk factor for stroke and chronic heart failure. Researchers at the NIH have discovered that administering a therapeutically effective dose of rhEPO or an EPO derivative, including carbamylated erythropoietin (CEPO) and Helix B surface peptide (HBSP), acutely reduces both systolic and diastolic blood pressure via Nitric Oxide (NO) signaling. Long-term administration of HBSP prevents elevation of arterial blood pressure in an animal model of hypertension. Unlike long-term treatment with rhEPO, administration of EPO derivatives, such as HBSP, does not stimulate excessive red cell production and will be useful in the development of anti-hypertensive drugs. CRADA Opportunity: The National Institute on Aging is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize a new anti-hypertensive drug based of non-erythropoietic derivatives of erythropoietin that combines vasodilative and tissue protective properties. For collaboration opportunities, please contact Vio Conley, M.S. at conleyv@mail.nih.gov. Click here to view the NIA collaborative opportunity announcement.

New Targeted Therapy for Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia

Mon, 10 Sep 2012 13:00:00 GMT
The invention describes the use of benzodiazepine compounds for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Specifically, the compounds can be used to treat core binding factor (CBF) leukemias, which are a subgroup of leukemia associated with the generation of fusion genes, arising from the binding between the transcription factors: core binding factor-beta (CBFbeta) and runt-related transcription factor 1 (RUNX1). The compounds described in this invention have been found to inhibit the binding of CBFbeta and RUNX1, resulting in selectively killing leukemia cells in culture and suppressing leukemia in a mouse model.

In addition, the binding of runt-related transcription factors from the RUNX family have been implicated in the development of other diseases, including (but not limited to): platelet disorders, solid tumours (e.g., lymphoma, breast cancer, osteosarcoma) and bone diseases (e.g., osteoporosis, cleidocranial dysplasia and intervertebral disk degeneration). Thus, the use of these compounds may represent new targeted therapies for AML and ALL as well as other RUNX-related disorders. CRADA Opportunity: The National Human Genome Research Institute (NHGRI), Oncogenesis and Development Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize benzodiazepine compounds described above to treat CBF leukemia, AML, ALL, and/or other RUNX-related disorders. Please contact Claire T. Driscoll, Director of NHGRI Technology Transfer Office (cdriscoll@mail.nih.gov; 301-594-2235) for more information.

Capillary Viscometer for Measuring Viscosity of Macromolecular Solutions of Biological Relevance

Mon, 10 Sep 2012 17:00:00 GMT
A capillary-based device and system for measuring the rheological properties of solutions of synthetic and biological polymers. The device automatically serially dilutes and varies the flow rate of a sample, permitting measurement of solution viscosity across wide ranges of concentration and shear rate without changing samples. The device can rapidly and accurately assay solute stability, solute-solvent and solute-solute interactions in solutions of proteins and other macromolecules of biotechnological and pharmaceutical interest, as well as solution injectability. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize automated capillary viscometer. For collaboration opportunities, please contact Allen P. Minton at minton@helix.nih.gov or Asaf Grupi at grupia@gmail.com.

Image Analysis Software for Quantitative Evaluation of Striation Patterns and their Defects in Skeletal Muscles

Mon, 10 Sep 2012 21:00:00 GMT
Available for licensing is software written in MatLab for evaluating striation patters in images of skeletal muscle fibers for better sensitivity in the quantitation of skeletal muscle disorders. Skeletal muscles have a regular, periodic organization (the periodicity of the sarcomeres), which is not only structural but also functional. Muscle pathologies create disorder in the normally periodic myofibrils. Objective grading of muscle morphology is necessary to assess muscle health, compare biopsies, and evaluate treatments and the evolution of disease. CRADA Opportunity: The Light Imaging Section of NIAMS, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize software for image analysis of cells and tissues and skeletal muscle. For collaboration opportunities, please contact Wenhua Liu at liuw5@mail.nih.gov or 301-451-4815.

Therapy for Cancer and Other Diseases Associated with Angiogenesis Driven by Vascular Endothelial Growth Factor-A

Thu, 30 Aug 2012 01:00:00 GMT
Vascular Endothelial Growth Factor-A (VEGF-A) is an angiogenic agent that drives blood vessel formation in solid tumors and other diseases, such as macular degeneration and diabetic retinopathy. Several therapies that target the ability of VEGF to stimulate angiogenesis have been approved. These therapies regulate VEGF-A activity by binding VEGF-A, thereby blocking VEGF-A from binding to its receptor on target cells. This technology utilizes a different approach to regulating VEGF-A activity by providing a VEGF-A protein antagonist that is produced by engineering native VEGF-A protein. The engineered VEGF-A protein disrupts heparan sulfate proteoglycan binding to the VEGF-A/VEGF receptor complex, an activity that is essential for the angiogenic properties of native VEGF-A. The antagonist has a binding affinity for both FLT-1 (VEGFR-1) and KDR/FLK-1 (VEGFR-2) that is equivalent to that of native VEGF-A and specifically antagonizes all VEGF-A-stimulated signaling events. CRADA Opportunity: The National Cancer Institute’s Urologic Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize antagonists to VEGF-A and hepatocyte growth factor (HGF) that block signal transduction and associated cellular responses by competitive displacement of native growth factors and concomitant disruption of heparan sulfate proteoglycan binding to the growth factor-receptor complex. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Enhanced Nanoparticle Cell-Entry for Cancer Therapy

Wed, 29 Aug 2012 05:00:00 GMT
Nanoparticles are being used as a method of drug delivery for the treatment of several diseases, cancer in particular. While the use and versatility of these particles have increased over the years, the speed with which these particles can enter the cells and deliver the drugs remains challenging.

This technology describes a method of modifying nanoparticles to markedly enhance their entry into cancer cells and their delivery of therapeutic drugs. The nanoparticles use a multi-shell calcium phosphate nanocore designed with target-specific siRNA and an endocytosis-enhancing agent. The inventors have shown that the intravenous systemic administration of the enhanced nanoparticles noticeably increases nanoparticle cell-entry along with concomitant delivery of siRNA to cancer cells in vivo. They further demonstrate that the composite calcium phosphate nanoparticle delivery of anti-cancer therapy can preferentially target in vivo tumors and cause tumor growth arrest. Consequently, these modified nanoparticles can exert a greater effect on cancer cells. CRADA Opportunity: The Kwong Laboratory, Surgery Branch, NCI, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize nanoparticles in anti-cancer therapy. For collaboration opportunities, please contact King F. Kwong, M.D. at kwongk2@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Context Aware Mobile Device Software for Substance Abuse Interventions and Behavioral Modification

Fri, 10 Aug 2012 09:00:00 GMT
Available for licensing for commercial development is software that provides personalized feedback for treating drug dependence and associated risky behaviors. The tool is designed for both healthcare providers at the point-of-care and for self-help. Many people who could benefit from treatment do not receive it because of its low availability and high cost. The available software “mPAL” (Mobile Personalized Assessment and Learning), combines mHealth-based educational functions with the Ecological Momentary Assessment (EMA) functions of TED (transactional electronic diary) software. mPAL allows interchange of data obtained from EMA and learning system in order to deliver context-aware intervention in real time, customized to the individual needs of participants. mPAL enables participants to interact with educational materials at the time and place of their choosing and receive personalized feedback when and where it is most needed. The software integrates into HuRlS where comprehensive patient data can be leveraged alongside the mPAL data to provide better understanding of the underlying factors under investigation. CRADA Opportunity: The NIDA, IRP, Biomedical Informatics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Mobile Personalized Assessment & Learning for Addiction Treatment and Behavioral Modification. For collaboration opportunities, please contact Vio Conley at conleyv@mail.nih.gov. Click here to view the NIDA collaborative opportunity announcement.

Quick2Insight: 3D Biological Tissue Image Rendering Software

Fri, 10 Aug 2012 13:00:00 GMT
Available for licensing for commercialization or internal use is software providing automatic visualization of features inside biological image volumes in 3D. The software provides a simple and interactive visualization for the exploration of biological datasets through dataset-specific transfer functions and direct volume rendering. The method employs a K-Means++ clustering algorithm to classify a two-dimensional histogram created from the input volume. The classification process utilizes spatial and data properties from the volume. Then using properties derived from the classified clusters the software automatically generates color and opacity transfer functions and presents the user with a high quality initial rendering of the volume data. User input can be incorporated through the simple yet intuitive interface for transfer function manipulation included in our framework. Our new interface helps users focus on feature space exploration instead of the usual effort intensive, low-level widget manipulation. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize automatic 3D visualization of biological image volumes. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin Domains Lacking Human B-cell Epitopes

Fri, 27 Jul 2012 17:00:00 GMT
Immunotoxins kill cancer cells while allowing healthy, essential cells to survive. As a result, patients receiving an immunotoxin are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins often leads to a reduced patient response due to the formation of neutralizing antibodies against immunogenic epitopes contained within Pseudomonas exotoxin A (PE). To improve the therapeutic effectiveness of PE-based immunotoxins through multiple rounds of drug administration, NIH inventors have sought to identify and remove the human B-cell epitopes within PE. Previous work demonstrated that the removal of the murine B-cell and T-cell epitopes from PE reduced the immunogenicity of PE and resulted in immunotoxins with improved therapeutic activity. This technology involves the identification and removal of major human B-cell epitopes on PE by mutation or deletion. Considering these immunotoxins will be administered to humans, the removal of human immunogenic epitopes is important. The resulting PE-based immunotoxins have increased resistance to the formation of neutralizing antibodies, and are expected to have improved therapeutic efficacy. CRADA Opportunity: The National Cancer institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Glial Cell Line-Derived Neurotrophic Factor Opposite Strand (GDNFOS) for Treatment of Neurodegenerative Diseases

Fri, 27 Jul 2012 21:00:00 GMT
Glial cell line-derived neurotrophic factor (GDNF) is a small human protein encoded by the GDNF gene. GDNF has been effective therapy in laboratory animal models of Parkinson's disease and protects several types of neurons in the brain and peripheral nervous system. The NIDA inventors have discovered primate-specific GDNFOS, encoded by the opposite strand of glial cell derived neurotrophic factor (GDNF) gene. The GDNFOS gene encodes for novel peptides that was found to be reduced in human middle temporal gyrus of Alzheimer's disease brains. These secreted growth proteins have potential neurotrophic activity and they might play a synergistic role in neuroprotective effects of GDNF in human brain. The NIDA inventors have also developed antibody against GDNFOS3 and generated compounds that have potential pharmaceutical use. The compounds consist of GDNFOS nucleic acid transcripts, GDNFOS protein or a functional fragment for treatment of human neurodegenerative diseases. CRADA Opportunity: The National Institute on Drug Abuse is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize GDNFOS peptide and non-coding RNAs as therapeutic agents for neurodegenerative diseases. For collaboration opportunities, please contact Vio Conley at conleyv@mail.nih.gov. Click here to view the NIDA collaborative opportunity announcement.

Salen-Manganese Compounds for Therapy of Viral Infections

Sat, 21 Jul 2012 01:00:00 GMT
Salen-manganese compounds are synthetic, stable, low toxicity, low cost agents that may provide protection from immune reaction-related oxidative cell damage associated with many illnesses. In particular, oxidative cell damage has been associated with many viral infections including influenza. This invention demonstrates that treating mice with salen-manganese compounds, after lethal pandemic influenza virus infection, significantly enhances survival. Salen-manganese treatment also reduces lung pathology and also improved cellular recovery and repair. Because oxidative damage is observed in many viral infections, administration of salen-manganese compounds may have therapeutic relevance to a wide range of viral infections, in addition influenza. Existing viral therapeutics merely target the infectious viral agent and not the damage caused by the immune system reaction related to infection. Because, salen-manganese treatments target the untapped therapeutic space of infection-induced, immune system-related pathology and have favorable safety and cost profiles, such therapies are ideal candidates for development. CRADA Opportunity: The NIAID Laboratory of Infectious Diseases, Viral Pathogenesis and Evolution Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Maryann Puglielli at 301-594-6656.

High-Affinity Mouse Monoclonal Antibodies To Glypican-3 for Cancer Treatment

Fri, 20 Jul 2012 05:00:00 GMT
Liver cancer is the fifth most common cancer in the world, with hepatocellular cancer (HCC) representing the preponderance of these liver cancers. As with many cancers, positive prognosis for a patient diagnosed with HCC correlates with the early detection of the disease. Unfortunately, HCC is usually detected at a late stage in its development, leading to poor prognosis for most patients. As a result, there is great interest and value in developing new agents which can detect the presence of HCC in a patient at an early stage.

Glypican-3 (GPC3) is a cell surface heparan sulfate glycoprotein that is expressed on the vast majority of HCC cells. The correlation between GPC3 expression and HCC makes GPC3 an attractive candidate for studying the disease progression and treatment of HCC. The presence, progression and treatment of this disease can potentially be monitored by tracking the level of expression of GPC3 on cells. This can be accomplished using monoclonal antibodies which recognize only GPC3, particularly the cell surface domain of the protein. This invention concerns the generation of several monoclonal antibodies that are specific for the cell surface domain of GPC3 (YP6, YP7, YP8, YP9 and YP9.1), and which can be used either as therapeutic candidates for treating GPC3-related diseases or as research reagents for studying the role of GPC3 in HCC. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize liver cancer therapy and diagnostics, humanization, antibody drug/toxin conjugates. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Novel Analogues of the Asthma Drug Fenoterol as Liver and Brain Cancer Therapeutic Agents

Fri, 20 Jul 2012 09:00:00 GMT
Available for licensing are specific fenoterol analogues, such as MNF, that inhibit the growth of various types of cancers, including brain, liver, colon, and lung tumors. MNF acts as an agonist of the GPRSS cannabinoid (CB) receptor and, as such, represents one of the first potential drugs directed at this target. MNF crosses the blood brain barrier and initial toxicity studies indicate that it has few off-target effects. These new analogues can be used to treat CB receptor related disorders and diseases, and in particular GRPSS-related disorders and diseases, including brain and liver cancers for which there are no current effective treatments. CRADA Opportunity: The IRP/NIA/LCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize (R,R')-4'-methoxy-1-naphthylfenoterol for the treatment of brain, liver and colon carcinomas. For collaboration opportunities, please contact Nicole Guyton, Ph.D. at darackn@mail.nih.gov. Click here to view the NIA collaborative opportunity announcement.

Individualized Cancer Therapy that Suppresses Tumor Progression and Metastasis Through Decreased Expression of TGF-beta Receptor II in Bone Marrow Derived Cells

Mon, 09 Jul 2012 13:00:00 GMT
Scientists at the NIH have developed a method of suppressing tumor progression and metastasis by targeting a pathway. This novel treatment method is an individualized therapy that first screens patients to determine if they are a candidate for the treatment, and then utilizes their own altered bone marrow to inhibit tumor progression.

Tumor inhibition is achieved through decreased expression of TGF-beta receptor II (TGFbeta r2) in bone marrow derived myeloid cells, which is essential in tumor metastasis. The inventors have devised a patient selection method whereby the patient's blood is drawn and screened for TGFbeta r2 expression, and those patients with above normal expression are candidates for treatment. After candidate screening the patient's bone marrow is harvested and divided into two parts: one part for cell culture and the other for storage and later use. The patient's cell culture bone marrow is treated to remove TGFbeta r2 in myeloid cells through either virus, non viral particle, or nanoparticle. The patient is treated with total body radiation and then receives an infusion of the treated cell culture bone marrow. After tumor metastasis is suppressed, the altered bone marrow is removed, and the stored bone marrow is returned to the patient. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize technologies including but not limited to RNAi viral particle or nanoparticle, or miRNA. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Antagonists of Hyaluronan Signaling for Treatment of Airway Inflammation and Hyperresponsiveness

Tue, 03 Jul 2012 17:00:00 GMT
Airway inflammation and hyperresponsiveness are hallmarks of airway disease. Investigators at NIEHS identified a new class of compounds that can block hyaluronan signaling and inhibit airway hyperresponsiveness and inflammation. Airway diseases, such as asthma and chronic obstructive airway disease, affect tens of millions of patients worldwide, and are chronic diseases with limited options for treatment (bronchodilators and inhaled steroids are the two classes of drugs currently in common use). Therefore, a novel class of treatment agents could have significant public health and market impact. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the use of hyaluronan antagonists to treat chronic respiratory diseases. For collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. at denholme@niehs.nih.gov.

Mouse-Derived NY-ESO-1 T Cell Receptor for Use in Immunotherapy

Tue, 03 Jul 2012 21:00:00 GMT
Scientists at the National Institutes of Health have developed a T cell receptor (TCR) derived from mouse T cells (i.e. murine TCR) that can be expressed in human T cells to recognize the cancer testis antigen (CTA), NY-ESO-1, with high specificity. This anti-NY-ESO-1 TCR has murine variable regions that recognize the NY-ESO-1 epitope and murine constant regions. The inventors performed in vitro studies comparing this murine NY-ESO-1 TCR with a previously developed human NY-ESO-1 TCR counterpart, which yielded promising clinical outcomes in patients with a variety of cancers. The murine TCR functioned similarly to the human counterpart in their ability to recognize and react to NY-ESO-1 tumor targets.

NY-ESO-1 is a CTA, which is expressed only on tumor cells and germline cells of the testis and placenta. CTAs are ideal targets for developing cancer immunotherapeutics, such as anti-CTA TCRs, because these TCRs are expected to target cancer cells without harming normal tissues and thereby minimize the harsh side effects associated with other types of cancer treatment. NY-ESO-1 is expressed on a wide variety of cancers, including but not limited to breast, lung, prostate, thyroid, and ovarian cancers, melanoma, and synovial sarcomas. Thus, this technology should be applicable in adoptive cell transfer therapies for many types of cancer. CRADA Opportunity: The NCI Surgery Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this murine NY-ESO-1 reactive TCR. For collaboration opportunities, please contact Steven A. Rosenberg, M.D., Ph.D. at sar@nih.gov. Click here to view the NCI collaborative opportunity announcement.

Benign Tissue or Malignant Tumors? Using CpG Dinucleotide Methylation Patterns to Diagnose Cancer in the Adrenal Glands and Adrenal Cortex

Wed, 04 Jul 2012 01:00:00 GMT

This technology represents new methods to distinguish malignant adrenocortical tumors from benign tumors and normal tissue in the adrenal glands/cortex using the methylation patterns of cytosine-phosphate-guanine dinucleotide (CpG) sequences. A biopsy or other noninvasive means of tissue or fluid collection to obtain patient nucleic acid can allow clinicians to test an individual's CpG methylation patterns to diagnose if the individual's sample is malignant and if a malignancy is a primary or metastatic adrenocortical tumor. Different CpG methylation patterns comparing normal/benign and malignant tissues may also serve as target sites for developing adrenocortical cancer therapies. Genes where increased CpG methylation is predictive of malignancy include KCTD12, KIRREL, SYNGR1, and NTGN2, as well as other secondary sequences.

Adrenal glands sit atop the kidneys and release stress response hormones. The CpG methylation patterns of 5-methylcytosines at CpG sites can alter gene expression, which can impact if a tumor will develop benign or malignant properties and influence its metastatic potential. Effective diagnosis of these tumors will improve adrenal cancer therapy and help avoid unnecessary surgery or chemotherapy for patients with benign tumors.
CRADA Opportunity: The National Cancer Institute Endocrine Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize a diagnostic method for adrenocortical cancer through analysis of methylation patterns in tissue. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Exposing T cells to Fas Ligand (FasL)-Fas Receptor (FasR) Antagonists Withholds Differentiation and Increases Expansion Making T cells More Suitable for Use in Cancer Immunotherapy

Tue, 03 Jul 2012 05:00:00 GMT
NIH scientists have developed methods to make a better immunotherapy by exposing T cells to Fas ligand (FasL) or Fas receptor (FasR) antagonists and agonists. Researchers have found that FasL-FasR antagonists suppress T cell differentiation leaving them in a naïve state. These T cells are a more ideal cell type for adoptive cell transfer therapies because they have not exhausted their effector functions and demonstrate greater proliferation, enhanced persistence and survival, and better activity against their target antigen when infused in vivo to treat cancer. Also, the prevention of T cell differentiation/effector function in vivo has implications for autoimmune diseases and syndromes. FasL-FasR agonists enhance T cell differentiation towards more effector-like cells. Enhancing the differentiation of T cells is expected to be useful in treating cell proliferation disorders, such as leukemias, lymphomas, or Wiskott-Aldrich syndrome.

FasL (or cluster of differentiation 95L) is a transmembrane protein in the tumor necrosis factor (TNF) family. FasR (or apoptosis antigen 1, CD95, or TNF receptor superfamily member 6) is a transmembrane protein belonging to the TNF receptor/nerve growth factor receptor superfamily. Normally, when FasL binds to FasR, a cell death signal is triggered in the cell. Antagonists of FasL-FasR interaction may include caspase inhibitors, mutated FasL/FasR, RNAi, or FasL/FasR antibodies. Agonists may include FasL/FasR encoding nucleotides. CRADA Opportunity: The Surgery Branch of the NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the prevention of T cell differentiation and effector function as part of Immunotherapy. For collaboration opportunities, please contact Steven A. Rosenberg, M.D., Ph.D. at sar@nih.gov. Click here to view the NCI collaborative opportunity announcement.

A3 Adenosine Receptor Agonists to Treat Chemotherapy-induced Peripheral Neuropathy

Wed, 13 Jun 2012 09:00:00 GMT
This invention claims species-independent agonists of A₃AR, specifically (N)-methanocarba adenine nucleosides and related pharmaceutical compositions. The A₃ adenosine receptor (A₃AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A₃AR subtype have been developed that are also selective for the mouse A₃AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A₃ versus A₁ in humans while retaining at least 400x selectivity for A₃ versus A₁ in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A₃ agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Marguerite J. Miller at 301-496-9003 or millermarg@niddk.nih.gov.

New Ammunition to Fight Cancer: The Rapid Isolation of Central Memory T Cells for Adoptive Immunotherapy

Wed, 13 Jun 2012 13:00:00 GMT
This technology is a new technique to rapidly isolate tumor-reactive central memory T cells in a highly enriched, non-invasive manner from the peripheral blood of cancer patients for cancer adoptive cell immunotherapy. Cells are drawn from a patient's blood, divided into subsets, and contacted with the tumor antigen of interest to identify T cells whose T cell receptor (TCR) recognizes the tumor antigen. Such T cells are identified by measuring the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) produced by the cells (i.e., the IL-2 index) using high-throughput quantitative PCR (HT-qPCR). NIH scientists have identified that cells with a specific IL-2 index consistently contain central memory T cells for the tumor antigen of interest.

Preclinical animal studies have suggested that central memory T cells can proliferate, persist, and survive better after adoptive transfer compared to other T cell types. They also show increased anti-cancer activity. Clinical trials using central memory T cells represent an important extension of these studies. Adoptive immunotherapy is showing promise as a cancer treatment, but one drawback to this method, prior to this invention, was the laborious and time consuming nature of the cell isolation process and the unpredictable and sometimes ineffective nature of the cells infused into patients. CRADA Opportunity: The Center for Cancer Research, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this novel technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Fast Acting Molecular Probes for Real-Time In Vivo Study of Disease and Therapeutics

Wed, 13 Jun 2012 17:00:00 GMT
This technology is for fast acting molecular probes made from a fluorescent quencher molecule, a fluorophore, an enzyme cleavable oligopeptide (for example targeted by protease) and FDA-approved polyethylene glycol (PEG) as well as associated methods to identify cell activity with these probes. Proteases regulate many cell processes such as inflammation as well as pathological processes in cancer and cardiovascular disease. High protease activity is associated with metastatic cancers. Proteases are also active in apoptosis, and tissue remodeling in cardiovascular disease. Although highly useful in vitro, conventional probes are unstable, nonspecific or slow activating in vivo. This new probe is faster than standard probes (30 min vs. 24 hrs) and has enhanced target-to background ratios. It enables quick screening of animals in an array of applications related to protease-associated diseases and other diseases. It may detect specific biological targets and monitor in vivo therapeutic efficacy in real time. Most drug candidates identified by in vitro screening fail in vivo. Failures are costly. Identifying in vivo drug efficacy sooner would reduce waste and increase successful drug development. CRADA Opportunity: The National Institute of Biomedical Imaging and Bioengineering is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize fast acting molecular probes for real-time in vivo study of disease and therapeutics. For collaboration opportunities, please contact Cecilia Pazman at pazmance@nhlbi.nih.

Software for Modeling Tumor Delivery and Penetration of Antibody-Toxin Anti-Cancer Conjugates

Wed, 13 Jun 2012 21:00:00 GMT
Available for licensing is software for modeling permeability and concentration of intravenously administered antibody anti-cancer agent conjugates in solid tumor. The models can be used to determine optimal dosing regimen of a therapeutic in a particular cancer type. Thirty factors that affect delivery rates and efficiencies are analyzed as variables in generating the models. CRADA Opportunity: The NCI, CCR, Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize targeted delivery of anti-cancer agents in solid tumors. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Endothelial Cell Line to Study Prevention of Atherosclerosis

Thu, 14 Jun 2012 01:00:00 GMT
Atherosclerosis underlies most cases of cardiovascular disease (CVD), which is now the major cause of morbidity and mortality in developed countries. An inflammatory reaction is an essential component in the appearance and development of an atherosclerotic lesion. The inflammatory process is associated with the expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) at the surface of endothelial cells. Antiatherogenic lipoprotein, high density lipoprotein (HDL), is known to down regulate the expression of VCAM. Increasing levels of HDL is a promising way to reduce the risk of CVD.

This technology is directed to the generation of a stable endothelial cell line expressing a luciferase reporter construct driven by the VCAM promoter. This reporter system enables an easier measurement of VCAM expression and determination of the effect of HDL on endothelial cell inflammation. This technology can be used to screen for the effect of drugs that modulate HDL metabolism and it is more convenient than doing Western blots. CRADA Opportunity: The Cardiovascular & Pulmonary Branch, NHLBI/NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize endothelial cells to study prevention of atherosclerosis. For collaboration opportunities, please contact Dr. Alan Remaley at aremaley1@cc.nih.gov.

Treatment of Viral Infection by Blocking Interleukin-21

Wed, 06 Jun 2012 05:00:00 GMT
Blocking interleukin (IL-21) may be an effective method to treat or prevent various viral infections. In the course of an immune response to a virus, IL-21, produced primarily by CD4+ T cells, can inhibit or stimulate (regulate), immune cell function (B cells, T cells, natural killer cells, dendritic cells). IL-21 regulation may be either protective or pathological; autoimmune disease pathology has been associated with IL-21 promoted inflammation (in: type 1 diabetes, lupus, and multiple sclerosis). This technology describes methods of blocking IL-21 that may reduce damaging inflammatory responses during certain viral infections. Specifically, the absence of IL-21 during respiratory viral infection such as pneumonia virus infection actually prevents some of the pathogenic effects that may be promoted by IL-21. Methods for controlling IL-21 signaling may be used to treat to prevent many pathological effects of pneumonia viruses, and other viral infections. CRADA Opportunity: The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize treatment of viral infection by blocking Interleukin-21 (E-017-2012). For collaboration opportunities, please contact Vincent Kolesnitchenko, Ph.D. at kolesniv@nhlbi.nih.gov.

Quantitative in vivo Methods to Estimate the Conduction Time of Nerve Impulses in the Brain

Thu, 24 May 2012 09:00:00 GMT
The axon diameter distribution (ADD) is an important anatomical feature of nerve fascicles both in normal and abnormal development. Axon diameter directly affects nerve function. It is well known that in myelinated axons, the conduction velocity is directly proportional to axon diameter. Moreover, it is hypothesized that in amyotrophic lateral sclerosis (ALS) large diameter axons are damaged selectively, while in autism, small-diameter axons are over-expressed. Despite its importance, the ADD within nerve fascicles has not been measurable in-vivo, and currently can only be assessed by invasive histological means. Previously, the NICHD inventors developed magnetic resonance imaging (MRI) methods to measure the ADD within nerve fascicles (e.g., by AxCaliber MRI). This invention extends from the inventor's prior work to AxCaliber MRI along with the non-invasive measurement of the arc-length of a nerve pathway (e.g., using DTI tractography), to estimate the mean conduction time of nerve impulses along that pathway, as well as other statistical moments of the conduction time distribution. This method could be used to diagnose abnormalities in nerve conduction in brain regions and providing a neuroanatomical basis for many cognitive and behavior disorders. CRADA Opportunity: The NICHD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize methods to estimate conduction time of nerve impulses in brain. For collaboration opportunities, please contact Charlotte McGuinness at mcguinnc@mail.nih.gov.

Low-dose Cardiac Computed Tomography Method for Whole Heart Extracellular Volume

Thu, 24 May 2012 13:00:00 GMT
Myocardial infarction and cardiomyopathies result in myocardial scar and diffuse fibrosis. Together these result in poor cardiac function. Myocardial scar is a specific target for therapy, but is difficult to identify. Cardiac Computed Tomography (CCT) struggles to identify large scars, and could not previously identify fibrosis. MRI is often used, but MRI is expensive and not widely available. We have developed a method to quantify both diffuse and focal myocardial scar by CCT using low radiation dose methods. Extracellular volume fraction (ECV) is the distribution of iodine in the scar relative to blood pool. ECV is abnormally elevated in scar. The new CCT technique involves a) CCT data about the myocardium and blood pool is extracted (via a shape constrained graph cut technique), b) an algorithm (Demons deformable registration) is applied to pre-contrast and low dose post-contrast image information, c) the ECV value is computed. Along with coronary artery depiction on CCT, the ECV can be used to quantitatively measure myocardial scar and diffuse myocardial fibrosis for a complete depiction of the patient's myocardial status/ health. CRADA Opportunity: The NIH Clinical Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Cardiac CT, Cardiac CTA, myocardial scar, myocardial fibrosis, coronary artery disease imaging. For collaboration opportunities, please contact Ken Rose, Ph.D. at rosek@mail.nih.gov.

Software for Automated Determination of Macromolecular Structure Using Cryo-electron Microscopy

Thu, 24 May 2012 17:00:00 GMT
Available for licensing is software for automated generation of density maps of macromolecular structures from series of 2D digital micrographs of frozen hydrated specimens collected using an electron microscope equipped with an ultra-cooled computerized stage. Series of images of biological specimens collected at different tilt angles relative to the electron beam are aligned to compensate for mechanical errors of the stage and combined to obtain 3D images (tomograms). Sub volumes containing a single macromolecular complex can be extracted from the 3D image of a protein solution, or suspension of viruses or cells. These individual sub-volumes of identical structures are aligned and averaged together to generate a density map of the macromolecular complex of interest. CRADA Opportunity: The NCI Laboratory of Cell Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Rabbit Polyclonal Antibody to Detect a Pro-peptide Fragment of NSAID-activated Gene (NAG-1)/GDF15, a Protein Associated with Cancer

Thu, 24 May 2012 21:00:00 GMT
Chronic inflammation is clearly associated with an increase in the risk of cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) are well documented as agents that inhibit tumor growth and with long-term use can prevent tumor development. NSAID-activated gene (NAG-1), a unique member of the TGF-beta superfamily, is highly induced by NSAIDs and numerous drugs and chemicals with anti-tumorigenic activities.

The protein product of NAG-1 is first formed into an immature peptide dimer that must be cut at a specific site before it can be secreted as a mature protein. Currently available antibodies can only detect either the immature form of NAG-1 or the secreted mature protein, but do not recognize the peptide fragment that remains when the immature dimer is cut to form the mature protein. Now available for the first time, the present new antibody recognizes this NAG-1 pro-peptide fragment. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this antibody. For collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. at denholme@niehs.nih.gov.

GLI-Similar 3(GLIS3) Knock Out (KO) Mice as Models to Screen Therapeutics for Diabetes, Polycystic Kidney Disease, and Hypothyroidism

Wed, 16 May 2012 01:00:00 GMT
GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis. To further identify and study the physiological functions of GLIS3, NIEHS investigators generated mice in which GLIS3 is ubiquitously knocked out (GLIS3-KO) or conditionally knocked out in a cell type-specific manner. GLIS3-KO mice develop polycystic kidney disease, hypothyroidism, and neonatal diabetes, as indicated by the development of hyperglycemia and hypoinsulinemia. The pancreatic endocrine cells, particularly insulin-producing pancreatic beta cells, are greatly diminished in these mice. The pancreas-selective knockout mice GLIS3(Pdx1-Cre) develop severe diabetes within 2-3 months, much later than the GLIS3-KO mice. The kidney-selective knockout of GLIS3 (GLIS3(Ksp-Cre) mice lack expression of GLIS3 in the collecting ducts and develop severe polycystic kidney disease within a period of 2-4 months. These mice can be used as models to screen therapeutics for diabetes, polycystic kidney disease, and hypothyroidism. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize GLIS3 Knock Out Mice. For collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. at denholme@niehs.nih.gov.

Methods for Selection of Cancer Patients and Predicting Efficacy of Combination Therapy with Histone Deacetylase (HDAC) and mTOR Inhibitors

Tue, 15 May 2012 05:00:00 GMT
Available for licensing is a novel gene signature of thirty-seven drug responsive genes that links changes in gene expression to the clinically desirable outcome of improved overall survival. Expression of these genes has been linked to prognosis in several cancers, including, but not limited to multiple myeloma, lung, breast, and melanoma. Patients identified by this signature would be predicted to benefit from combined HDAC inhibitor/mTOR inhibitor therapy. Additional information is available upon request. CRADA Opportunity: The NCI Center for Cancer Research, Laboratory of Cancer Biology and Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Methods for Selecting Cancer Patients for HDACi/mTORi Combination Therapy. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Human DNA Polymerase Gamma for Testing the Effect of Drugs on Mitochondrial Function

Wed, 09 May 2012 09:00:00 GMT
One of the primary means for treating HIV infection is the use of antiviral nucleotide or nucleoside analogs. These analogs work by inhibiting the activity of reverse transcriptase, the enzyme responsible for preparing the HIV genome for integration into the DNA of the host cell. Although these analogs do not have an effect on the polymerases responsible for replicating the human genome, the polymerase responsible for replicating the mitochondrial genome is sensitive to these analogs. When patients are exposed to nucleotide or nucleoside analogs through long-term treatment regimens, the replication of the mitochondrial genome can be adversely affected. Since mitochondrial functionality is necessary for cell activity, the nucleotide and nucleoside analogs can cause serious and unwanted side-effects.

This invention concerns the cloning and purification of human DNA polymerase gamma, the polymerase responsible for replicating the mitochondrial genome. The enzymes that have been purified include the wild-type version, a version which lacks exonuclease (proofreading) activity, and several versions with modified activity due to the mutation of the enzyme. These purified enzymes can be used to directly test the effects of new drugs that affect the activity of polymerases, such as nucleotide and nucleoside analogs. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the antibodies. For collaboration opportunities, please contact Elizabeth Denholm at denholme@niehs.nih.gov.

Multilayer X-Ray Transmission Grating Array for Phase-Contrast Imaging and Tomography

Wed, 09 May 2012 13:00:00 GMT
Classical X-ray Computed Tomography (CT) and radiography are based on X-ray absorption and cannot show soft tissue structures as well as Magnetic Resonance Imaging (MRI). Detecting the phase delay/advance of X-rays that travel through the body could enhance soft tissue contrast 10 - 100 times. Submicron-period X-ray transmission gratings for medical x-ray energies can substantially enhance the phase detection sensitivity, but fabrication is a great challenge. This invention includes a method to fabricate multilayer transmission gratings of large areas. The design uses multilayer deposition of alternating materials on a staircase substrate to form micro grating arrays of extremely small periods and high aspect ratio in large areas. This invention should substantially improve the visibility of soft tissue structures and reduce radiation dose to patients. CRADA Opportunity: The Imaging Physics Lab, Biophysics and Biochemistry Center, NHLBI/NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize multilayer-coated gratings for phase-contrast CT. For collaboration opportunities, please contact Dr. Han Wen at wenh@nhlbi.nih.gov.

Transgenic Hspa2-Cre Mice for Studying Spermatogenesis and Male Infertility

Fri, 04 May 2012 17:00:00 GMT
HSPA2 is a member of the HSP70 family of heat-shock proteins that serve as molecular chaperones. Hspa2-cre expression mimics the spermatogenic cell-specific expression of endogenous HSPA2 within the testis, being first observed in leptotene/zygotene spermatocytes. Expression of the transgene is also detected at restricted sites in the brain, as occurs for endogenous HSPA2.

Researchers at NIEHS developed the first transgenic mouse line that expresses Cre-recombinase under the control of the promoter of the heat shock protein A2 (Hspa2) gene. Expression of the Hspa2-Cre transgene during meiosis in male germ cells makes these mice a useful tool for defining the roles of genes expressed at different times during spermatogenesis or expressed in spermatogenic cells. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this mouse strain. For collaboration opportunities, please contact Elizabeth Denholm, Ph.D. at denholme@niehs.nih.gov.

Hspa2 Knockout Mice for Study of Spermatogenesis and Male Infertility

Fri, 04 May 2012 21:00:00 GMT
HSPA2 is a member of the HSP70 family of heat-shock proteins that serve as molecular chaperones. Researchers discovered that HSPA2 protein is expressed in spermatogenesis during the meiotic phase. Spermatogenic cells lacking the HSPA2 protein arrest in mid-meiosis and undergo apoptosis. HSPA2 is present in the synaptonemal complex of wild-type mice and the chromosomes fail to separate in HSPA2-deficient mice (previously known as Hsp70-2-/- mice), suggesting that HSPA2 is required for the chromosomal events of meiosis such as synapsis, crossing over, or recombination.

Researchers at NIEHS developed a knockout strain of mice in which the heat shock protein gene (Hspa2) is disrupted. This mouse model is useful in studying the process of spermatogenesis and the influence of various environmental toxins or drugs on sperm production and male infertility. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this mouse strain. For collaboration opportunities, please contact Elizabeth Denholm, Ph.D. at denholme@niehs.nih.gov.

Novel Reduced Toxicity Tropolone Derivative Compounds That Have Anti-Viral Activity Through Inhibiting RNase H Activity

Wed, 02 May 2012 01:00:00 GMT
Several novel tropolone derivatives have been identified that inhibit HIV-1 RNase H function and have potential for anti-viral activity due to reduced cellular toxicity. Inhibiting RNase H function is a potential treatment for many viral infections, since RNase H function is essential for viral replication for many pathogenic retroviruses such as HIV-1 and HIV-2. Although many hydroxytropolone compounds are potent RNase H inhibitors biding at the enzymatic active site, they are limited as therapeutic candidates by their toxicity in mammalian cells. The toxicity thought to be a result of inhibition of multiple essential mammalian metalloenzymes. We reasoned that the potential beneficial application of tropolone RNase H inhibition might be of therapeutic use if the toxic effects in mammalian cell were eliminated. By selectively adding steric bulk to add new drug-enzyme contacts for the RNase H active site, a number of novel compounds, that have initially demonstrated reduced cytotoxicity, have been produced. Importantly, these novel compounds appear to retain antiviral activity essential for use as therapeutics. CRADA Opportunity: The Molecular Targets Laboratory, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize antiviral tropolone derivatives developed by systematic medicinal chemistry on the lead series. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

A Broadly Neutralizing Human Anti-HIV Monoclonal Antibody (10E8) Capable of Neutralizing Most HIV-1 Strains

Tue, 01 May 2012 05:00:00 GMT
This Human Anti-HIV Monoclonal Antibody (10E8) has great potential to provide passive protection from infection, as a therapeutic vaccine, or as a tool for the development of vaccine immunogens. 10E8 is one of the most potent HIV-neutralizing antibodies isolated thus far and it can potently neutralize up to 98% of genetically diverse HIV-1 strains. 10E8 is specific to the membrane-proximal external region (MPER) of the HIV envelope protein, GP41. It is anticipated that 10E8 could be used in combination with another human anti-HIV-1 monoclonal antibody to provide an antibody response that neutralizes nearly all strains of HIV-1. Additionally, 10E8 is a useful tool for the design of vaccine immunogens that can elicit an adaptive immune response to produces 10E8 like antibodies. This technology also includes monoclonal antibodies from the same germ line as 10E8. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize vaccine immunogens capable of eliciting a 10E8-like adaptive immune response. For collaboration opportunities, please contact Bill Ronnenberg at 301-451-3522 or wronnenberg@niaid.nih.gov.

Chimeric Antigen Receptors that Recognize BCMA/ CD269 for Treating Multiple Myeloma

Mon, 30 Apr 2012 09:00:00 GMT
Available for licensing are chimeric antigen receptors (CARs) that specifically target B-cell maturation antigen (BCMA, CD269), a protein that is highly expressed on the surface of multiple myeloma cells. Multiple myeloma is a malignancy of plasma cells. It is almost always incurable.

A CAR is a fusion protein that can recognize a specific protein on a tumor cell and activate an adaptive immune response to attack the tumor cell. When cultured with multiple myeloma cells in vitro, T-cells engineered to express the CARs were able to induce cell death in the myeloma cells. CARs currently are being evaluated in clinical trials as a promising new area of cancer therapy. The technology available for licensing includes vectors incorporating the CARs, as well as methods of destroying multiple myeloma cells using T-cells engineered to express a CAR. CRADA Opportunity: The National Cancer Institute, Experimental Transplantation and Immunology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize chimeric antigen receptors to genetically-modify T cells to recognize BCMA/ CD269. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov.

Monoclonal Antibodies Targeting Human DNA Polymerase beta, a DNA Repair Enzyme

Thu, 19 Apr 2012 13:00:00 GMT
Available for licensing are monoclonal antibodies targeting human DNA polymerase beta (Pol B). Pol B is a constitutively expressed "housekeeping" enzyme that plays a role in base excision repair (BER), a cellular defense mechanism that repairs DNA base damage and loss. Aberrant Pol B expression is associated with genomic instability indicating that Pol B is required for DNA maintenance, replication and recombination.

These antibodies can be utilized to elucidate BER's mechanism of action and Pol B's structure and function. Moreover, the antibodies can be used to detect Pol B in samples with a variety of techniques including immunoblotting, ELISA, immunoprecipitation, and immunohistochemistry. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize these monoclonal antibodies. For collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. at denholme@niehs.nih.gov.

Cytochromes P450 CYP2J and CYP2C Polyclonal Antibodies and Recombinant Proteins

Wed, 18 Apr 2012 17:00:00 GMT
The National Institutes of Health announces polyclonal antibodies against mouse cytochrome P450s CYP2J and CYP2C. Cytochrome P450s catalyze the metabolism of a wide range of exogenous compounds, including drugs, industrial chemicals, environmental pollutants, and carcinogens. The 2C family of cytochrome P450 metabolizes an extensive number of drugs which include tolbutamide, S-Warfarin, mephenytoin, diazepam and taxol. Many of the P450 enzymes are also active in the NADPH-dependent oxidation of arachidonic acid to various eicosanoids found in several species. The 2J family is expressed at high levels in the heart and has been shown to metabolize both arachidonic acid and linoleic acid. The CYP2J and CYP2C subfamily members have a wide tissue distribution and may be useful as model systems for studies of cardiovascular disease, drug metabolism and toxicity.

Recombinant proteins of mouse cytochrome P450s CYP2C and CYP2J have also been expressed and can be used as controls in immunoblotting, as well as for metabolism studies. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize antibodies against mouse cytochrome P450s CYP2J and CYP2C. For collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. at denholme@niehs.nih.gov.

Treatment of Acute and Chronic Neurological Disorders Using GLP-1, Exendin-4 and Analogs

Wed, 18 Apr 2012 21:00:00 GMT
Glucagon-like peptide-1 (GLP-1) and related peptides, including exendin-4 and liraglutide, are incretin mimetics that enhance glucose-dependent insulin secretion following food ingestion as a regulator of glucose homeostasis. Exendin-4 and liraglutide are used clinically in the safe and effective treatment of type 2 diabetes to enhance insulin secretion and maintain a euglycemic state. These actions are primarily mediated at the level of the GLP-1 receptor in the pancreas; however, these compounds are known to enter the brain where the GLP-1 receptor also is expressed.

Researchers at the NIH have discovered the novel use of GLP-1 and exendin-4 analogs in the treatment of acute and chronic neurological disorders and neurodegenerative diseases. Studies conducted in extensive cell culture and in mouse models using these analogs have demonstrated significant neurotrophic and neuroprotective actions in models of several disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS, stroke, head trauma and peripheral neuropathy. These studies have now been extensively published and independently validated by other scientific groups. Furthermore, clinical studies are ongoing to evaluate the use of GLP-1 receptor agonists for the treatment of early Alzheimer's disease, Parkinson's disease and diabetic neuropathy by several groups within the US and Europe. CRADA Opportunity: The National Institute on Aging, Drug Design and Development Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Vio Conley at conleyv@mail.nih.gov.

Nonpathogenic Bacteria, Paenibacillus alvei, Useful as a Natural Biocontrol Agent for Elimination of Food-borne Pathogenic Bacteria

Tue, 10 Apr 2012 01:00:00 GMT
This newly isolated non-pathogenic bacterial strain (TS-15) has shown the ability to kill or inhibit a wide variety of harmful bacteria including many of the most common food-borne pathogens such as Salmonella, Escherichia, Listeria, Shigella, Enterobacter and Staphylococcus. The TS-15 stain may provide a natural low cost means to help protect the food supply. The strain may be used as a biocontrol agent in the form of a pesticide or pretreatment to soils in which fruits and vegetable are grown. Preventative use of the TS-15 strain in biocontrol measures may prevent many of the millions of illnesses in the U.S. that are caused by food-borne pathogens each year. Such prevention may also reduce the associated costs of treatment for such illnesses. Furthermore, isolation and development of the antibiotic compounds produced by the TS-15 strain may yield useful new compositions to help treat bacterial illness, including infections by some pathogens resistant to standard antibiotics. CRADA Opportunity: The FDA Center for Food Safety and Applied Nutrition is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Paenibacillus alvei (TS-15). For collaboration opportunities, please contact Alice Welch at alice.welch@fda.hhs.gov.

Potential Use of anti-IgE in the Treatment of Lupus Nephritis

Tue, 27 Mar 2012 05:00:00 GMT
Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease characterized by a significant morbidity and mortality related to both disease evolution as well as therapeutic side effects. At least half of SLE patients develop lupus nephritis.

The inventors have used a Lyn -/- mouse model that develops an autoimmune disease exhibiting some features of human SLE. Using this model the inventors identified basophils and self-reactive IgEs as important components in the development of autoantibody-mediated kidney disease. The inventors found that depletion of basophils or the absence of IgE causes a considerable reduction in autoantibody production and preserves kidney function in the Lyn -/- mice. The inventors' work demonstrates that IgE immune complexes can activate basophils and that removal of self-reactive IgEs that form functional circulating immune complexes prevents kidney disease. Further, the inventors have shown that basophils are contributors to the production of the self-reactive antibodies that cause lupus-like nephritis in the Lyn -/- mice. Accordingly, reducing circulating IgE levels or reducing basophil activation may be of therapeutic benefit. CRADA Opportunity: The National Institute of Arthritis and Musculoskeletal and Skin Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the technology for the use of anti-IgE in the treatment of Lupus Nephritis. For collaboration opportunities, please contact Cecilia Pazman at pazmance@mail.nih.gov.

Novel Diagnostic, Prognostic and Therapeutic Biomarker for Hepatocellular Carcinoma

Tue, 27 Mar 2012 09:00:00 GMT
Scientists at the National Cancer Institute have discovered that Stearol-CoA desaturase-1 (SCD-1) is associated with hepatocellular carcinoma (HCC). Utilizing a microarray to analyze HCC patient samples, the investigators found SCD-1 is elevated in liver tumor tissues and it is a marker for a highly aggressive form of HCC, hepatic stem cell-like HCC subtype (HpSC HCC), which retains stem-cell features capable of cellular plasticity and cell motility. The investigators found SCD-1 is significantly elevated in HpSC tumors in comparison to less aggressive HCC tumors and it is associated with poor patient survival. In vitro studies demonstrate SCD-1 inhibition and/or addition of saturated palmitic acid reduces HpSC HCC characteristics. In addition to diagnostic, prognostic, and treatment applications, this technology may enable clinicians to effectively stratify patients for more aggressive cancer treatment and prioritize candidates for liver transplantation. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize biomarkers for liver cancer. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human Tumors

Tue, 27 Mar 2012 13:00:00 GMT

Scientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have enhanced ability to generate cytotoxic T-lymphocytes (CTL), which in turn have a greater ability to kill MUC-1 expressing human tumor cells. The agonist epitopes span both the VNTR region of MUC-1 and the C-terminus region. The epitopes encompass two major MHC alleles reflecting the majority of the population.

Along with the method of use, the technology encompasses the use of these agonist epitopes in peptide- and protein-based vaccines, with dendritic cells or other antigen presenting cells, or encoding sequences in DNA, viral, bacterial, yeast, or other types of vectors, or to stimulate T-cells in vitro for adoptive immunotherapy protocols.

The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers. The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.
CRADA Opportunity: The Laboratory of Tumor Immunology and Biology, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the use of MUC-1 tumor antigen agonist epitopes for the treatment or prevention of cancer. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

A Novel, Non-invasive Test for the Detection of Chromaffin Cell Tumors Associated with SDHB Mutation

Fri, 23 Mar 2012 17:00:00 GMT
Pheochromocytomas/ paragangliomas (PHEOs/PGLs) are hormone producing tumors of the sympathetic nervous system located in the adrenal glands (which sit atop the kidneys) or the paraganglia, which are distributed throughout the upper body. Mutations in the gene of a mitochondrial protein, succinate dehydrogenase B (SDHB), can cause PHEOs/PGLs that have a high rate of malignancy. Normally, PHEOs/PGLs can be diagnosed by measuring increased stress hormone metabolites in blood or urine. However, detection of SDHB-related PHEOs/PGLs can be difficult as up to ten percent do not show elevated stress hormone metabolites, and thus proper diagnosis requires expensive and often not-widely-available imaging. In addition, SDHB-PHEO/PGL patients need regular imaging to rule out development of metastases and family members of patients with SDHB-PHEOs/PGLs need genetic testing for risk evaluation. A significant need remains for additional diagnostic methods to prevent misdiagnosis of patients with non-secreting or metastatic SDHB-PHEOs/PGLs and risk evaluation of family members.

Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have developed methods to identify SDHB mutation based on the presence/ absence of just four urinary peptides. Further data from the researchers suggests that metastatic PGLs can also be identified in patients based on their urinary peptide pattern. CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize a urine-based diagnostic to detect proteins associated with pheochromocytoma/paraganglioma (PHEO/PGL). For collaboration opportunities, please contact Joseph M. Conrad III, Ph.D., J.D. at jmconrad@mail.nih.gov.

Use of Englerin A, a Small Molecule HSF1 Activator, for the Treatment of Diabetes, Obesity, and Other Diseases Associated with Insulin Resistance

Fri, 23 Mar 2012 21:00:00 GMT
Insulin resistance is a causative factor for type 2 diabetes, obesity and a number of other conditions. This technology claims methods for treating diseases or conditions associated with insulin resistance using the small molecule epoxy-guaiane derivative englerin A and related compounds. The compounds are claimed separately in a related NIH technology.

The inventors have shown that englerin A, a compound originally isolated from the Phyllanthus plant and previously identified as an anti-cancer agent, can also be used to treat insulin resistance. Insulin resistance is associated with reduced gene expression and production of heat shock protein 70 (HSP70). Using a mouse with tumor model, the inventors discovered that administration of englerin A decreases blood glucose levels by activating transcription of HSF1, thereby increasing the expression and secretion of HSP70. Thus, englerin A and related compounds represent potential drugs for the treatment of a variety of conditions associated with insulin resistance. CRADA Opportunity: The NCI Urologic Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize epoxyguaianes as anti-type 2 diabetes agents. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov.

Direct Impact Spark Ionization (DISI) Mass Spectrometry (MS) for Identification of Microbes

Sat, 24 Mar 2012 01:00:00 GMT
Generating reproducible mass spectra from bacterial samples in a timely fashion at atmospheric pressure remained problematic for many years. FDA/NCTR inventors designed a rapid mass spectrometry device using direct impact spark ionization source for microbial analytes identification via spectral pattern recognition. The device design includes a rapid mass spectrometer suitable for analyzing microbiological samples that was earlier used to analyze low volatile organic compounds. The device employs a solid needle for electrode discharge. It includes a gear plate that introduces stainless steel pins carrying bacterial samples. The pins also act as counter electrodes and are targeted by controlled arcs. The small custom-made glass cylinder that is meant to shut out oxygen and prevent the introduction of ambient moisture into the analyte is unique from other DISI device. The examination revealed enormous peak intensity and spectral information with normal ionization mode on the same instrument. This device can be employed in fields such as pathogen determination in clinical settings, QA/QC (of drugs, food or cosmetic ingredients), continuous monitoring of (airborne) Biological Warfare Agents and the like. CRADA Opportunity: The NCTR/FDA inventors are seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this device. For collaboration opportunities, please contact Alice Y. Welch, Ph.D. at Alice.Welch@fda.hhs.gov.

Personalized Body Weight Management System Using Monitoring Devices and Mathematical Models of Metabolism

Fri, 23 Mar 2012 05:00:00 GMT
Attempts to manage body weight are often unsuccessful or only temporary. This is, in part, due to antiquated dieting methods that attempt to address calorie consumption while ignoring metabolic and physical changes. It is becoming clear that personalized methods to manage body weight must be developed.

Scientists at the NIH have developed new methods for prescribing and monitoring personalized weight management interventions. The system uses validated mathematical models of human metabolism to set weight management goals and predict individual body weight outcomes in the context of changing metabolic needs and calorie consumption. The system uses repeated monitoring of a patient's body weight to assess progress and provide specific feedback to the patient and health care professional. Projected outcomes and body weight goals can be revised over time along with required prescription modifications to meet the body weight goals. The system is integrated into a network of one or more devices that may additionally monitor various physiological parameters, physical activities, food intake, or other behaviors. Such an enhanced personalized weight management program has great promise in the management of obesity. CRADA Opportunity: The NIDDK Laboratory of Biological Modeling is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Marguerite J. Miller at 301-496-9003 or millermarg@niddk.nih.gov.

The Cancer Stem Cell Finder: A Novel Reporter Construct which uses Transposition and Green Fluorescent Protein Expression to identify Cancer Stem Cells

Fri, 02 Mar 2012 10:00:00 GMT
Scientists at the National Institutes of Health (NIH) have designed a novel reporter construct which can be used to identify, monitor, and allow for the manipulation of cancer stem cells (CSCs). CSCs are a subset of poorly differentiated tumor cells expressed at low frequency within a tumor and are resistant to conventional chemotherapies. CSCs have high metastatic potential and give rise to new tumors that spread cancer throughout the body. These characteristics make CSCs prime targets for developing new therapeutic agents to eradicate cancer.

The reporter construct is a novel expression vector composed of the Sleeping Beauty transposon plasmid and a Nanog promoter linked to green fluorescent protein (GFP). Nanog is a transcription factor that is overexpressed in embryonic stem (ES) cells and tumors that resemble ES cells. When introduced into a population of tumor cells, the Nanog-GFP-Sleeping Beauty transposon construct is able to integrate into tumor cell DNA via transposition. If the transposed cell is a CSC, the Nanog transcription factor overexpressed in that CSC will bind to the Nanog-promoter in the reporter construct to drive GFP expression within the cell. Thus, CSCs can be isolated based on their selective expression of the GFP label. The NIH scientists have utilized their reporter construct to identify small populations of CSCs in mouse and human breast cancer cell models. CRADA Opportunity: The Cancer and Inflammation Program, NCI, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Nanog promoter driven GFP constructs for the easy identification and isolation of cancer stem cells. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Small-Molecule Inhibitors of Human Galactokinase for the Treatment of Galactosemia and Cancers

Fri, 02 Mar 2012 15:00:00 GMT
Lactose, found in dairy products and other foods, is comprised of two simple sugars, glucose and galactose. In galactosemia, where galactose is not properly metabolized, build-up of toxic compounds, such as galactose-1-phosphate, can lead to liver disease, renal failure, cataracts, brain damage, and even death if this disorder is left untreated. Currently, the only treatment for galactosemia is elimination of lactose and galactose from the diet, but in some cases this is not sufficient to avoid long-term complications from the disorder.

This technology describes selective small-molecule inhibitors of human galactokinase, which inhibit the first step in galactose metabolism. These compounds could be used to treat galactosemia by eliminating the build-up of toxic metabolites in brain, liver and other tissues, and could form the basis for the first effective treatment for this disorder.

These inhibitors are also promising candidates for the treatment of certain cancers, such as PTEN/AKT misregulated cancers. The inventors have already shown that the inhibitors are cytotoxic for several cancer cell lines. CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Small-Molecule Inhibitors of Human Galactokinase for the Treatment of Galactosemia and Cancers. For collaboration opportunities, please contact Lili M. Portilla, MPA at portilll@mail.nih.gov.

Novel Radio-labeled Agents for Imaging Alzheimer's Disease-associated Amyloid

Mon, 27 Feb 2012 20:00:00 GMT
This technology introduces novel radio-labeled agents for imaging amyloid deposits in the brains of Alzheimer's Disease patients. These are small molecule, radio-ligand compounds that are analogs of benzo[d]thiazole. They are highly specific to amyloid, have low background noise, do not undergo rapid defluoridation and do not produce residual radioactivity in the brain. In addition, the compounds are stable and may be readily synthesized from commercially available starting materials. These compounds may be used in many noninvasive imaging techniques including: magnetic resonance spectroscopy (MRS) or imaging (MRI), or positron emission tomography (PET) or single-photon emission computed tomography (SPECT) to measure amyloid. Non-invasive detection of Alzheimer's disease-associated amyloid plaques in the brain would be valuable for early diagnosis, monitoring, and for clinical development of therapeutic drugs. CRADA Opportunity: The National Institute of Mental Health (NIMH) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Beta-amyloid Imaging Agents. For collaboration opportunities, please contact Suzanne L. Winfield, Ph.D. at winfiels@intra.nimh.nih.gov or 301-402-4324.

A Method of Identifying Cdk5/p35 Modulators, and Possible Diagnostic or Therapeutic Uses for Neurodegenerative Diseases

Sat, 25 Feb 2012 01:00:00 GMT
Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine cyclin-dependent kinase that is highly expressed in the central nervous system and controls many biological processes that impact learning and memory, as well as pain and drug addiction. Studies have indicated that abnormal Cdk5 activity may be associated with the onset of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). The kinase activity of Cdk5 is turned on when it binds to one of the two proteins considered to be neuronal activators, p35 and p39.

Scientists at the NIH designed a cell-based assay to screen for p35 transcriptional regulators that work as upstream regulators of Cdk5. This technology may be useful for assessing the presence and risk of conditions associated with atypical Cdk5 kinase activity or for finding drug modulators that could be promising drug targets. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Laboratory of Cell and Developmental Biology, Functional Genomics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

Human sRAGE Protein for Treating Vascular Disease, Injury, or Inflammation

Thu, 23 Feb 2012 06:00:00 GMT

Methods of producing soluble receptors for advanced glycation end products (sRAGE) with enhanced expression, the resulting modified molecules, and methods of using this highly potent sRAGE for treating adverse vascular conditions. The inventors established a way to produce human sRAGE with more than 1000-fold greater potency than current methods. Production of full length human sRAGE in cultured mammalian cells enables the addition of mammalian post-translational modifications that dramatically enhance potency.

The receptor for advanced glycation end products (RAGE) is a cell surface protein that triggers signaling pathways leading to inflammation. RAGE-stimulated inflammation can contribute to adverse vascular conditions, such as atherosclerosis and restenosis. The soluble version of RAGE (sRAGE) binds the same target molecules (advanced glycation end products), but cannot activate inflammatory signaling pathways. For this reason, sRAGE is thought to act as a decoy for RAGE. sRAGE reduces inflammation and pathogenic consequences associated with RAGE signaling.
CRADA Opportunity: The National Institute on Aging, Laboratory of Cardiovascular Science, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize sRAGE. For collaboration opportunities, please contact Vio Conley, M.S. at conleyv@mail.nih.gov. Click here to view the NIA collaborative opportunity announcement.

Use of Frizzled (Fzd) as a Biomarker for Cancer Patient Selection and Therapeutic Intervention

Thu, 23 Feb 2012 11:00:00 GMT
Personalized medicine is becoming more important in the diagnosis and treatment of diseases, particularly cancer. One signaling pathway which has been demonstrated to be involved in cancer is the Wnt/beta catenin signaling pathway. The NIH scientists associated with this technology have identified a potential new biomarker for cancer based on their investigation of the role of the secreted frizzled related proteins, sFRP's, which are known to play a role in Wnt/beta catenin signaling. In particular, the scientists have determined that different Frizzled receptors (Fzd) have different and opposite roles in Wnt/beta catenin signaling with the expression of certain Fzd receptors, e.g. Fzd5, being associated with an increase in Wnt/beta catenin signaling and the expression of other Fzd receptors, e.g., Fzd2, being associated with a decrease in Wnt/beta catenin signaling. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Regulation of Wnt and Frizzled signaling by secreted Frizzled-related proteins. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov.

miR126 for the Mobilization of Hematopoietic Stem/Progenitor Cells (HSPCs) into Peripheral Blood

Thu, 23 Feb 2012 16:00:00 GMT
The NIH inventors have discovered that a micro RNA, miR126, mobilizes hematopoietic stem/progenitor cells (HSPCs) from the bone marrow into blood. These mobilized HSPCs can be easily collected from blood and used for reconstitution of ablated or functionally-impaired bone marrow. miR126 may also facilitate mobilization of bone-resident cancer cells into the circulation where they could be more easily targeted by cancer therapeutics. This discovery could replace bone marrow transplantation as we do it today. Rather than using the current non-selective agent G-CSF (which preferentially mobilizes mature myeloid cells rather than stem/progenitor cells), miR126 could be used for selective mobilization of the HSPCs needed for hematopoietic cell transplantation. Additionally, miR126 could be used to mobilize malignant cells from the bone marrow and render them more easy targets for therapy. It was previously shown that the bone marrow cavity promotes the survival of many cells including tumor cells, and that such cells may easily die when removed from the bone marrow niche and moved to the blood. Therefore, this discovery could also change treatment of many cancers that arise within the bone marrow or metastasize to the bone. Since the mechanism by which miR126 promotes HSPCs/tumor cell mobilization is attributable to the inhibition of VCAM-1 expression, miR126 could be used to treat inflammatory states where the expression of VCAM1 provides an anchor for inflammatory cells at sites of inflammation. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize miR126 and Mobilization of Hematopoietic Stem/Progenitor Cells. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

A New Class of Broad-spectrum Antibiotics: Naturally-occurring Chrysophaetins and Their Analogues

Wed, 22 Feb 2012 21:00:00 GMT
This invention, offered for licensing and commercial development, relates to a new class of naturally occurring antimicrobial compounds called Chrysophaetins, and to their synthetic analogues. Isolated from an alga species, the mechanism of action of these compounds is through the inhibition of bacterial cytoskeletal protein FtsZ, an enzyme necessary for the replication of bacteria. FtsZ is responsible for Z-ring assembly in bacteria, which leads to bacterial cell division. Highly conserved among all bacteria, FtsZ is a very attractive antimicrobial target.

The chrysophaetin exhibits antimicrobial activity against drug resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), as well as other drug susceptible strains. The general structure of the natural compound is shown below:

CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the chrysophaentin antibiotics. Please contact Marguerite J. Miller at 301-451-3636 or millermarg@niddk.nih.gov for more information.

Non-toxic Compounds that Inhibit the Formation and Spreading of Tumors

Thu, 23 Feb 2012 02:00:00 GMT
Available for licensing are novel pyrrolopyrimidine compounds that disrupt the assembly of the perinucleolar compartment (PNC), a sub-nuclear structure highly prevalent in metastatic tumors. These notable compounds act without overt cytotoxicity.

The presence of the PNC positively correlates with metastatic capacity, making it a potential marker for cancer development and prognosis. These compounds could also serve as useful tools to elucidate the biology driving the formation and maintenance of the PNC, and unravel its association with metastasis. CRADA Opportunity: The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Lili M. Portilla, MPA at 301-217-2589 or Lilip@nih.gov.

Antagonists of the Hedgehog Pathway as Therapeutics for the Treatment of Heterotopic Ossification, Vascular Calcification, and Pathologic Mineralization

Mon, 13 Feb 2012 07:00:00 GMT
Heterotopic ossification (HO) results from osteoid formation of mature lamellar bone in soft tissue sites outside the skeletal periosteum (skeletal system), most commonly around proximal limb joints. HO can also be caused by genetic diseases such as progressive osseous heteroplasia (POH) and fibrodysplasia ossificans progressiva (FOP). Currently, all forms of HO lack adequate treatments and definite cure. Vascular calcification is a complex process that involves biomineralization and resembles osteogenesis. It is exacerbated during such conditions as diabetes, osteoporosis, menopause, hypertension, metabolic syndrome, chronic kidney disease, and end stage renal disease. In the present technology, the inventors describe novel methods for preventing or treating HO and vascular calcification using one or more antagonists of the Hedgehog pathway. The inventors, using both in vitro (limb culture experiments) and in vivo studies using Prx1-cre; Gsf/f mice model discovered that the antagonists of the Hedgehog pathway prevent formation of HO. The inventors also observed that Prx1-cre; Gsf/f mice developed calcification or mineralization around their blood vessels, and treatment with Hedgehog antagonists reduced mineralization throughout the body of these mice, including regions around the blood vessels, as observed by mineral staining. The antagonists that can be used to develop effective therapeutics include zerumbone epoxide, arcyriaflavin C, 5,6-dihyroxyarcyriaflavin A, physalin F, physalin B, arsenic trioxide (ATO), sodium arsenite, etc. CRADA Opportunity: The National Human Genome Research Institute (NHGRI) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize antagonists of the Hedgehog pathway for treatment of ossification and calcification disorders. For collaboration opportunities, please contact Claire T. Driscoll at 301-594-2235 or cdriscoll@mail.nih.gov.

Influenza Vaccine

Mon, 13 Feb 2012 12:00:00 GMT
It has been shown that the fusion peptide, a sequence comprised of fourteen amino acids at the N-terminal of the influenza hemagglutinin 2 protein, is conserved among A and B influenza viruses. Monoclonal antibodies against this peptide are capable of binding all influenza virus HA proteins and inhibit viral growth by impeding the fusion process between the virus and the target cell. This application claims immunogenic conjugates comprising the fusion peptide region linked to a carrier protein. In preclinical studies, these conjugates were immunogenic and induced booster responses. The induced antibodies bound to the recombinant HA protein. This methodology of linking the highly conserved fusion peptide region to a carrier protein can broaden the protective immune response to include influenza A and B virus strains. This would eliminate the need for annual influenza vaccination. CRADA Opportunity: The NICHD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize conjugate influenza vaccines comprising fusion peptide region. For collaboration opportunities, please contact Joseph Conrad, Ph.D., J.D. at 301-435-3107 or jmconrad@mail.nih.gov. Click here to view the NICHD collaborative opportunity announcement.

Chimeric Antigen Receptors to CD22 for Treating Hematological Cancers

Mon, 13 Feb 2012 17:00:00 GMT
Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause some T-cells to become cytotoxic. Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize. Thus, by engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target cells for destruction. This is a promising new therapeutic approach known as adoptive cell therapy.

CD22 is a cell surface protein that is expressed on a large number of B-cell lineage hematological cancers. Several promising therapies are being developed which target CD22, including therapeutic antibodies and immunotoxins. This technology concerns the use of a high affinity antibody binding fragment to CD22 as the targeting moiety of a CAR, adding adoptive cell therapy as a new prospective treatment for certain leukemias and lymphomas. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Chimeric Antigen Receptor for CD22, High Affinity. A gene vector to target T cells to B cell leukemia and lymphoma. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Ketamine Metabolites for the Treatment of Depression and Pain

Wed, 08 Feb 2012 22:00:00 GMT
The market continues to have a need for therapeutics for treating pain and depression that have efficacy in a high percentage of patients but have reduced anaesthetic properties and reduced abuse liability. Ketamine, a drug currently used in human anesthesia and veterinary medicine, has been shown in clinical studies to be effective in the treatment of several conditions, including the of treatment-resistant bipolar depression, major depressive disorder, neuropathic pain, and chronic pain, including complex regional pain syndrome (CRPS). However the routine use of the drug is hindered by unwanted central nervous system (CNS) effects and a patient response rate of ~70%. New data suggests that ketamine metabolites can be used with similar results but with an increase in patient response rates and a decrease in undesirable side effects. CRADA Opportunity: The National Institute on Aging, Laboratory of Clinical Investigation, Bioanalytical Chemistry and Drug Discovery Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Nicole Guyton, Ph.D. at darackn@mail.nih.gov. Click here to view the NIA collaborative opportunity announcement.

Modulating Autophagy as a Treatment for Lysosomal Storage Diseases

Wed, 18 Jan 2012 03:00:00 GMT
Researchers at NIAMS have developed a technology for treatment of lysosomal storage diseases by inhibition of autophagy. Pompe disease is an example of a genetic lysosomal storage disease caused by a reduction or absence of acid alpha-glucosidase (GAA). Patients with Pompe disease have a lysosomal buildup of glycogen in cardiac and skeletal muscle cells and severe cardiomyopathy and skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme replacement therapy is quite ineffective for the skeletal muscle myopathy. Skeletal muscle resistance to therapy is associated with increased cellular buildup of autophagic debris. Inactivation of autophagy results in effective GAA replacement therapy and a reduction in glycogen back to normal levels. This technology provides a novel approach for the treatment of Pompe disease as well as other diseases where autophagy is a critical contributor to disease development. CRADA Opportunity: The National Institutes of Health is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the technology for disabling autophagy as a treatment for lysosomal storage diseases. For collaboration opportunities, please contact Cecilia Pazman at pazmance@mail.nih.gov.

Monospecific and Bispecific Human Monoclonal Antibodies Targeting IGF-II

Tue, 17 Jan 2012 08:00:00 GMT
The type 1 insulin-like growth factor (IGF) receptor (IGF1R) is over-expressed by many tumors and mediates proliferation, motility, and protection from apoptosis. Agents that inhibit IGF1R expression or function can potentially block tumor growth and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed by multiple tumor types. Previous studies indicate that inhibition of IGF-I, and/or IGF-II binding to its cognizant receptor negatively modulates signal transduction through the IGF pathway and concomitant cell proliferation and growth. Therefore, use of humanized or fully human antibodies against IGFs represents a valid approach to inhibit tumor growth. The present invention discloses two monoclonal antibodies, designated m610.27 and m630, and a bispecific monoclonal antibody, m660, generated by linking domains from m610.27 and m630. All three antibodies display high affinities for IGF-I and IGF-II in the pM to nM range. The antibodies inhibited signal transduction mediated by the IGF-1R interaction with IGF-I and IGF-II and blocked phosphorylation of IGF-IR and the insulin receptor. m610.27 and m630 are the first pair of human antibodies that target nonoverlapping epitopes on IGF-II. All three antibodies in an IgG1 or IgG1-like format could lead to irreversible elimination of IGF-II from circulation making it a viable candidate for cancer treatment. CRADA Opportunity: The NCI CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov.

New Cholera Vaccine and Method for Conjugating Bacterial Polysaccharides to Proteins

Mon, 09 Jan 2012 13:00:00 GMT
A new conjugate vaccine for cholera has been developed. The invention includes a new method to conjugate the O-specific polysaccharide-core part of the bacterial lipopolysaccharide and protein subcomponents. Conventional technology has entailed chemical treatment of both components to introduce linkers, which made them amenable for covalent linking. The new method simplifies production by utilizing squaric acid chemistry for conjugating the free amine-containing species (e.g. polysaccharides) directly to amine-containing species (e.g. proteins) without prior modification of either component. While demonstrated in this new cholera prototype vaccine, the technology is envisioned as generally applicable, thereby streamlining a complex production process. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize conjugate vaccines. For collaboration opportunities, please contact Marguerite J. Miller, M.B.A. at 301-496-9003 or millermarg@niddk.nih.gov.

Immunogenic Tetrasaccharide of Anthrax Spores

Mon, 09 Jan 2012 18:00:00 GMT
The subject of this invention is a conjugate vaccine against Bacillus anthracis the causative agent of anthrax. Substantial effort has been made to study the structure and antigenic elements of the outermost layer of B. anthracis spores. The exosporium is fully exposed to the external environment. Analysis of isolated exosporia shows as many as 20 protein components of which the most prominent is the Bacillus collagen-like protein of anthracis (BclA), a glycoprotein that displays a unique tetrasaccharide capped at its upstream end with a novel sugar residue termed anthrose. Rabbit IgG antibodies elicited by B. anthracis spores specifically recognize this tetrasaccharide. The anthrose-containing saccharide may be linked to acceptable protein carriers using standard chemistry.

Subsequent to this work, the laboratory has demonstrated that squaric acid chemistry may be a more efficient chemistry than is currently used to connect the carbohydrate and protein portions of the vaccine. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize conjugated vaccines. For collaboration opportunities, please contact Marguerite J. Miller, M.B.A. at 301-496-9003 or millermarg@niddk.nih.gov.

Novel Small Molecules to Treat Alzheimer's Disease: Amyloid Beta Channel Blockers with Anti-inflammatory Properties

Fri, 06 Jan 2012 23:00:00 GMT
Alzheimer's Disease (AD) is a common, chronic neurodegenerative disease which is thought to be due to the neurotoxic effect of the Amyloid beta (Abeta) peptide. The inventors discovered that Abeta has intrinsic calcium channel activity, and that entry of calcium into neurons through this channel leads to neuronal cell death, playing a role in Alzheimer's Disease pathology. Consistently, Abeta channel blocking drugs act as a “cork” to save neurons from Abeta-dependent cell death. Two potent and efficacious candidate drugs, MRS2481 and its enantiomeric species MRS2485, have been discovered. Both block the Abeta channel with similar potency (ca. 500 nM) and efficacy (100%). However, inhibition by MRS2481 is easily reversible, while inhibition by MRS2485 is virtually irreversible. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize a small molecule drug to treat Alzheimer's Disease. For collaboration opportunities, please contact Marguerite J. Miller, M.B.A. at 301-496-9003 or millermarg@niddk.nih.gov.

One Step Fluorine-18 Peptide Labeling Strategy of Biological Substrates

Fri, 09 Dec 2011 04:00:00 GMT
A one-step process is now available for licensing that allows direct 18F labeling of any biological substrate that is modified with 4-nitro-3-trifluoromethyl arene. Normally, 18F labeling requires several time-consuming radio synthesis steps using prosthetic groups, resulting in a low labeling yield. Other attempts at one step labeling methods have also shown relatively low yields.

This new process eliminates time-consuming radiosynthesis steps and associated low labeling yields with a single step process that displaces a nitro group in an arene. Relatively low amounts of precursor and short time radiosynthesis times are required compared to direct peptide-labeling. Higher yields by this simplified process improve time and cost efficiencies and may make 18F labeling more amenable for automation. CRADA Opportunity: The NIBIB is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the technology for One Step Fluorine-18 Peptide Labeling Strategy of Biological Substrates. For collaboration opportunities, please contact Shawn Chen, Ph.D. at shawn.chen@nih.gov.

Mucus Shaving Apparatus for Endotracheal Tubes

Thu, 08 Dec 2011 09:00:00 GMT
HHS seeks parties interested in manufacturing and commercializing an endotracheal tube cleaning apparatus for insertion into the inside of the endotracheal tube of a patient to shave away mucus deposits. This cleaning apparatus comprises a flexible central tube with an inflatable balloon at its distal end. Affixed to the inflatable balloon are one or more silicone rubber shaving rings, each having a squared leading edge to shave away mucus accumulations implicated in bacterial accumulation. In operation, the un-inflated cleaning apparatus is inserted into the endotracheal tube until its distal end is properly aligned with the distal end of the endotracheal tube. After proper alignment, the balloon is inflated by a suitable inflation device (e.g., a syringe) until the balloon's shaving rings are pressed against the inside surface of the endotracheal tube. The cleaning apparatus is then pulled out of the endotracheal tube and in the process the balloon's shaving rings shave off the mucus deposits from the inside of the endotracheal tube. CRADA Opportunity: The NHLBI Pulmonary Critical Care Medicine Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the endotracheal tube mucus cleaning device and related laboratory interests. Please contact Marianne Lynch at 301-594-4094 or lynchm@nhlbi.nih.gov for more information.

Chemotoxins for Targeted Treatment of Diseased Cells

Fri, 02 Dec 2011 14:00:00 GMT
Researchers at the National Institute on Aging (NIA) have developed a straightforward method to elicit immune responses to specific cancers and AIDS by using a chemoattractant-based antigen delivery strategy. The strategy uses formulations composed of chemokines fused to toxic moieties (aka “chemotoxins”) to preferentially and specifically eliminate chemokine receptor-expressing cells. The method uses the natural ability of the chemokines to stimulate measurable and improved humoral and immune responses.

Chemokines can be of viral or microbial (B-Defensin) origin.

This method can also be used to cause inflammation to specifically target immune cells to increase immunogenicity for malignant tumors using SPANX-B and Laminin tumor antigens.

CRADA Opportunity: The National Institute on Aging (NIA) is seeking parties interested in collaborative research to further evaluate or commercialize effective vaccines that target bacterial, viral, or tumor antigens. Any or all of the inventions in this announcement are available for co-development and collaboration. For collaboration opportunities, please contact Nikki Guyton, Ph.D. at darackn@mail.nih.gov. Click here to view the NIA collaborative opportunity announcement.

AAV Mediated CTLA-4 Gene Transfer to Treat Sjogren's Syndrome

Fri, 18 Nov 2011 19:00:00 GMT
Sjögren’s syndrome is an autoimmune disease that affects over 2 million Americans, primarily over the age of 40. One of the major outcomes of Sjögren's syndrome is xerostomia (dry mouth) that is caused by immune system attack on moisture producing salivary glands. Researchers at the National Institute of Dental and Craniofacial Research have developed a therapy that alleviates xerostomia in a murine model of Sjögren's syndrome. This technology consists of a local delivery of adeno-associated virus (AAV) mediated cytotoxic T-lymphocyte antigen 4 Immunoglobulin-G (CTLA4IgG) fusion protein to salivary glands. The system effectively blocks CTLA4 ligand interactions with T cell surface receptors, resulting in immune suppression and reversal of autoimmune-related xerostomia. Targeted delivery of the AAV-CTLA4-IgG system makes this invention a novel therapeutic for the prevention of xerostomia-associated pain and discomfort caused by Sjögren's syndrome. CRADA Opportunity: The NIDCR is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact David Bradley at bradleyda@nidcr.nih.gov.

Treatment of Tuberculosis — Adjuvant Therapies to Increase the Efficiency of Antibiotic Treatments

Sat, 19 Nov 2011 00:00:00 GMT
There is growing evidence that resistance to Mycobacterium tuberculosis infection is governed in large part by the regulation of host cell death. Lipid mediators called eicosanoids are thought to play a central role in this process. The subject invention is a novel method of enhancing the efficacy of antibiotic treatments for Mycobacterium tuberculosis infection by co-administering an inhibitor of 5-lipoxygenase and a COX-2 dependent prostaglandin. Inhibition of 5-lipoxygenase and treatment with prostaglandin E2 results in alteration of the eicosanoid balance. The synergistic effects of altering the eicosanoid balance and treatment with antibiotics is believed to result in more efficient reduction of the bacterial burden and thus, the period of antibiotic administration and antibiotic dosage could potentially be reduced. In vivo data from mouse models can be provided upon request. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize adjuvant therapy for antibiotic treatment regiments against tuberculosis. For collaboration opportunities, please contact Katrin Mayer. Ph.D. at mayerk@niaid.nih.gov or 301-594-8061.

Genetically Engineered Mouse Model for Use as an Alternative Screening Method for Evaluating P-glycoprotein (P-gp) Substrate Toxicity in Avermectin-sensitive Dogs

Fri, 18 Nov 2011 05:00:00 GMT
A pitfall to avermectins is central nervous system (CNS) toxicities in herding dogs. As a result, all new avermectins must be tested in a "Collie Safety Study" to determine the degree of CNS toxicity. The toxicity is due to a 4 base pair mutation in the ATP-binding cassette, sub-family B member 1 (ABCB1) gene. This gene encodes for the P-glycoprotein (P-gp) that affects absorption, distribution and elimination of certain drugs. Researchers at FDA have developed an alternate animal model that includes two transgenic mouse models, one containing the mutant form of the canine ABCB1 gene (Yancy 1 line) and the other containing the canine wild-type gene (Yancy 2 line). The paired mouse system can be utilized to assess the safety of avermectins and other canine drugs by determining the toxicity to canines with the mutated form of the ABCB1 gene. Ivermectin, a derivative of the avermectin family of heartworm drugs used to treat and control parasitic infections, was used to verify this mouse model. This technology will enhance the population predictions derived from clinical safety data and serve to reduce the use of dogs in avermectin derivative safety studies that are part of the Investigational New Animal Drug (INAD) approval process. CRADA Opportunity: The FDA Center for Veterinary Medicine is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this alternative mouse model. For collaboration opportunities, please contact Haile F. Yancy at haile.yancy@fda.hhs.gov or 301-210-4096.

Medical Device for Intraocular Injection of Therapeutics and Fluid Sampling

Wed, 16 Nov 2011 10:00:00 GMT
The National Institutes of Health seeks research collaboration and commercialization partners for a medical device for administering therapeutics into the eye to treat a variety of ocular diseases including diabetic retinopathy, retinal vein occlusion and macular degeneration. The device is a dual function needle that can both inject and sampling ocular fluid at the same injection site. The needle includes a hub portion in communication with a needle portion through a lumen that may be used as a conduit to inject a therapeutic into an injection site. A sample chamber, with an optional absorbent material, is disposed in the lumen capable of absorbing intraocular fluid via a passive filling action into the sample chamber. CRADA Opportunity: The National Eye Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize intraocular therapeutic delivery. For collaboration opportunities, please contact Alan E. Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov.

PANVAC — Cancer Vaccine for the Prevention and Treatment of Colorectal Cancer

Fri, 28 Oct 2011 14:00:00 GMT
Cancer immunotherapy is an approach where tumor associated antigens (TAAs), which are primarily expressed in human tumor cells, and not expressed or minimally expressed in normal tissues, are employed to generate a tumor-specific immune response. Specifically, these antigens serve as targets for the host immune system and elicit responses that results in tumor destruction. The initiation of an effective T-cell immune response to antigens requires two signals. The first one is antigen-specific via the peptide/ major histocompatibility complex and the second or “costimulatory” signal is required for cytokine production, proliferation, and other aspects of T-cell activation.

The PANVAC technology employs avirulent poxviruses to present a combination of tumor-associated antigens (TAAs) and costimulatory molecules to activate T-cells and break the immune systems tolerance towards cancer cells. This is performed using recombinant poxvirus DNA vectors that encode both T-cell costimulatory molecules and TAAs. The combination of the costimulatory molecules B7.1, ICAM–1 and LFA–3, is known as TRICOM. Recombinant poxviral vaccines (vaccinia (V) and fowlpox (F) containing TRICOM have been evaluated in prime (V)/boost (F) regimens in preclinical models and in several clinical trials in patients with metastatic colorectal cancer. Additionally, PANVAC has shown promising survival results in treating patients with metastatic colorectal cancer.

Furthermore, recombinant poxviral TRICOM based vaccines can also be employed for the prevention and/or therapy of colorectal cancer containing a range of other TAAs such as the T-box transcription factor Brachyury.

This technology is available for both licensing and collaborative research. A detailed announcement was published in the Federal Register on Thursday, October 27, 2011 (76 FR 66728), and may be viewed at http://www.gpo.gov/fdsys/pkg/FR-2011-10-27/pdf/2011-27859.pdf. CRADA Opportunity: A CRADA partner for the further codevelopment of this technology specifically in colorectal cancer is currently being sought by the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI. The CRADA partner will (a) generate and characterize recombinant poxviruses expressing specific tumor-associated antigens, cytokines, and/or T-cell costimulatory factors, (b) analyze the recombinant poxviruses containing these genes with respect to appropriate expression of the encoded gene product(s), (c) supply adequate amounts of recombinant virus stocks for preclinical testing, (d) manufacture and test selected recombinant viruses for use in human clinical trials for colorectal cancer, (e) submit Drug Master Files detailing the development, manufacture, and testing of live recombinant vaccines to support the NCI-sponsored IND and/or company-sponsored IND, (f) supply adequate amounts of clinical grade recombinant poxvirus vaccines for clinical trials conducted at the NCI Center for Cancer Research (CCR), and (g) provide adequate amounts of vaccines for extramural clinical trials, if agreed upon by the parties, and conduct clinical trials under company-sponsored or NCI-sponsored INDs. NCI will (a) provide genes of tumor-associated antigens, cytokines and other immunostimulatory molecules for incorporation into poxvirus vectors, (b) evaluate recombinant vectors in preclinical models alone and in combination therapies, and (c) conduct clinical trials for colorectal cancer of recombinant vaccines alone and in combination therapies.

Contact Michael Pollack at 301-435-3118 or email pollackm@mail.nih.gov for additional information about this CRADA opportunity.

Antiandrogen Small Molecules for the Treatment of Prostate Cancer

Fri, 21 Oct 2011 18:00:00 GMT
The present licensing opportunity is for a new class of small molecule compounds, and the method of using them to treat prostate cancer. This year it is estimated there will be over 32,000 deaths from prostate cancer showing an unmet need for a more effective treatment particularly for castrate-resistant prostate cancer (CRPC). CRPC is characterized by androgen-independent cancer cells that have adapted to the depletion of hormones and continue to grow. Abnormal androgen receptor signaling is known to drive advanced castrate-resistant prostate cancer. The small molecule compounds of the instant invention are antiandrogens that target androgen receptor signaling in both androgen-independent and androgen-sensitive androgen receptor activity, and androgen receptors that are resistant to the current antiandrogens available. Unlike the currently available antiandrogens, the new small molecules induce androgen receptor degradation and cell death in prostate cancer cells. Further, these compounds and methods can also induce degradation of other steroid hormone receptors demonstrating the possibility of treating a wider range of cancers. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Small Molecules for the Treatment of Prostate Cancer. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov or 301-496-0477.

Protease Deficient Bacillus anthracis with Improved Recombinant Protein Yield Capabilities

Fri, 21 Oct 2011 22:00:00 GMT
Species of Bacillus, such as Bacillus anthracis, Bacillus cereus, and Bacillus subtilis, are attractive microorganisms for recombinant protein production in view of their fast growth rate, high yield, and ability to secrete produced products directly into the medium. Bacillus anthracis is also attractive in view of its ability to produce anthrax toxin and ability to fold proteins correctly. This application claims a B. anthracis strain in which more than one secreted protease is inactivated by genetic modification. Such a protease-deficient B. anthracis has an improved ability to produce recombinant secreted proteins compared to other bacteria, particularly other Bacillus. Improvements include production of intact (i.e., mature full-length) proteins, often at high yield. CRADA Opportunity: The NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize B. anthracis vaccines, B. anthracis protein production. For collaboration opportunities, please contact Charles Rainwater at 301-435-8617.

Infectious Hepatitis E Virus Genotype 3 Recombinants – Prospective Vaccine Candidates and Vector System

Fri, 07 Oct 2011 02:00:00 GMT
This technology is a recombinant, infectious genotype 3 Hepatitis E virus (HEV) that has been adapted to grow in cell culture and can potentially be used to develop vaccines against HEV or as a vector system to insert exogenous sequences into HEV. The virus (strain Kernow-C1, genotype 3) originated from a chronically infected human subject and was adapted to grow in human hepatoma cells. The adapted virus is unique in that it contains an insertion of a portion of a human ribosomal protein in Open Reading Frame 1 of the virus. Desired exogenous sequences can potentially be placed in lieu of the insert without inactivating the virus.

Infection by HEV is a relevant health issue in a number of developing countries and is also an emerging food-borne disease of industrialized countries. Genotype 1 and 2 infections are found exclusively in humans while genotype 3 and 4 viruses have been found not only in humans, but also swine, deer, mongoose, cattle, and rabbits. In particular, genotype 3 and 4 viruses are ubiquitously found in swine and undercooked pork is thought to be one of the sources of infection for cases of human infections in industrialized countries. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize hepatitis E virus vaccines. For collaboration opportunities, please contact Maryann Puglielli, Ph.D., J.D. at 301-451-6863 or maryann.puglielli@nih.gov.

Human Phospho-Serine134 Glucocorticoid Receptor Polyclonal Antibody: Useful for the Characterization of Glucocorticoid Signaling Processes, e.g., in Cancer and Inflammation

Thu, 06 Oct 2011 06:00:00 GMT
The glucocorticoid receptor (GR) functions as a hormone-dependent transcription factor that is involved in the maintenance of basal and stress-related homeostasis. Serine 134 is a newly discovered phosphorylation target on the human glucocorticoid receptor that becomes phosphorylated during stress-activating conditions such as ultraviolet irradiation, nutrient starvation, and oxidative stress. The inventors have developed a rabbit polyclonal antibody that specifically recognizes the Ser 134 phosphorylated form of the human glucocorticoid receptor. This antibody may be particularly useful for a variety of basic research applications, such as the characterization and study of glucocorticoid signaling in cancer, inflammation, and other diseases.

The antibody is available as crude antisera and has been epitope purified; it has cross reactivity with human, rat, and mouse tissues. CRADA Opportunity: The NIEHS, Molecular Endocrine Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Human Phospho-Serine134 Glucocorticoid Receptor Polyclonal Antibody. Please contact Elizabeth M. Denholm at denholme@niehs.nih.gov for more information.

Diagnostic Assays and Methods of Use for Detection of Filarial Infection

Thu, 29 Sep 2011 10:00:00 GMT
The effort targeting the mosquito borne neglected tropical disease lymphatic filariasis for elimination through mass drug administration by 2020 will require accurate, cost effective methods for detecting early infections. The World Health Organization-recommended immunochromatographic test detects adult Wuchereria bancrofti (Wb) antigen in blood, but shows variable efficacy due to the complex life cycle of the parasites and cross reactivity with other organisms. This variability may hinder effective lymphatic filariasis elimination efforts. This new technology improves available detection methods through use of an isolated immunoreactive antigen, Wb123, from infective stage larvae (L3) Wb; which results in specific detection early in the infective cycle with reduced cross reactivity. This technology may see wide application in testing and surveillance of lymphatic filariasis as part of the effort to eliminate the disease worldwide. CRADA Opportunity: The National Institute of Allergy and Infectious Disease (NIAID) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Diagnostic Assays and Methods of Use for Detection of Filarial Infection. For collaboration opportunities, please contact Johanna Schneider, Ph.D. at Schneiderjs@niaid.nih.gov or 301-451-9824.

Rapid Molecular Assays for Specific Detection and Quantitation of Loa Loa Microfilaremia

Thu, 29 Sep 2011 14:00:00 GMT
The risk of fatal reactions in some infected individuals administered drug treatments for Loa loa infection, and the lack of accurate, convenient, diagnostics for this infection have thwarted efforts to eradicate the disease. Time consuming, labor intensive and training intensive microscope-based analysis of blood samples is the standard available diagnostic for Loa loa infection. This new assay technology introduces an easy to use, species-specific, highly sensitive, diagnostic that is able to be performed with minimal training. Positive test results may be indicated by an easily visualized color change and this test may be run without the need for expensive equipment such as a thermocycler. Because this test is rapid, cost efficient, labor efficient, accurate, and simple to run and read, it may be readily incorporated into portable point-of-care formats. These attributes make it ideally suited for use in locations where Loa loa infection is endemic. These advantages may lead to this technology becoming the new standard for diagnosis of Loa loa infections and a valuable tool, in control programs, to identify risks for adverse treatment reactions. CRADA Opportunity: The National Institute of Allergy and Infectious Disease (NIAID) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Rapid Molecular Assays for Specific Detection and Quantitation of Loa Loa Microfilaremia. For collaboration opportunities, please contact Johanna Schneider, Ph.D. at Schneiderjs@niaid.nih.gov or 301-451-9824.

Humanized Monoclonal Antibodies Efficient for Neutralization of Tick-Borne Encephalitis Virus (TBEV)

Thu, 29 Sep 2011 18:00:00 GMT
TBEV causes serious illnesses from meningitis to meningo-encephalitis, totaling 3,000 cases of hospitalization in Europe and between 5,000-10,000 cases in Russia reported every year. The Far Eastern hemorrhagic TBEV strains are associated with a mortality rate (between 1-2%), higher than other strains isolated in the Siberia or Western Europe. There is a high proportion (up to 46%) of TBEV patients with temporary or permanent neurological sequelae. The number of TBEV infections has increased steadily and TBEV cases have been reported in new areas, probably reflecting an increased spread of vector tick species. Prevention of TBEV infections has been carried out in a few countries in Europe by immunization using an inactivated TBEV vaccine. The vaccine carries a high manufacturing cost and requires a regimen of multiple doses, and for this reason, vaccination is not generally carried out. The materials disclosed are humanized monoclonal antibodies derived from TBEV-neutralizing Fab antibodies isolated from infected chimpanzees by repertoire cloning. One antibody in particular, MAb 2E6, has been demonstrated to bind to and neutralize a TBEV/dengue type 4 virus chimera (via interaction with the TBEV antigenic determinants) as well as the related Langat virus. Protection against TBEV/DEN-4 infection and Langat infection has been demonstrated using animal models of infection. The antibodies disclosed, in particular MAb 2E6, have the potential for use as prophylactic and therapeutic agents against TBEV and Langat virus. Additionally, these antibodies may be suitable as diagnostic reagents for the detection of TBEV and/or Langat virus. CRADA Opportunity: The NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize TBEV monoclonal antibodies. For collaboration opportunities, please contact Wade Williams at 301-827-0258.

Pharmaceutical Compounds for the Treatment of Spinal Muscular Atrophy and Other Uses

Tue, 20 Sep 2011 22:00:00 GMT
The SMA Project (http://www.smaproject.org/programs.html) was established by NINDS to identify new compounds with improved effectiveness, safety, and pharmacokinetic characteristics aimed at finding a new therapeutic treatment for Spinal Muscular Atrophy (SMA), a paralyzing and often fatal disease of infants and children. The result of the SMA Project medicinal chemistry optimization effort is a library of ~1400 indoprofren analogues with drug like properties. A lead pre-clinical candidate for SMA has been identified based on several factors, including its ability to increase SMN expression.

The mechanism by which these compounds affect ribosomal fidelity proves to be useful for many genetic CNS diseases. The ability of these compounds to read through nonsense stop codons, coupled with the ability to cross the blood-brain barrier and drug like properties, makes these compounds attractive as therapeutics for diseases such as Muscular Dystrophy and Cystic Fibrosis. Preliminary results in HIV and HPV assays show that these compounds potently inhibit viral replication, presumably via inducing ribosomal frame shift, suggesting potential for antiviral therapy. In addition, these compounds have been shown to be non-toxic and well-tolerated at high doses in rodents. CRADA Opportunity: The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize treatment for SMA. For collaboration opportunities, please contact Melissa Maderia at maderiam@mail.nih.gov.

A Novel Optomechanical Module that Enables a Conventional inverted Microscope to Provide Selective Plane Illumination Microscopy (iSPIM)

Wed, 31 Aug 2011 02:00:00 GMT
The invention describes an optomechanical module that, when engaged with a conventional inverted microscope, provides selective plane illumination microscopy (iSPIM). The module is coupled to the translational base of the microscope whereby a SPIM excitation objective is engaged to one portion of the mount body, and a SPIM detection objective (having a longitudinal axis perpendicular to that of the excitation objective) is engaged to another portion of the mount body. Such a system offers the advantages of SPIM (optically sectioned, high-speed volumetric interrogation of living samples, enabling, for example, the study of developmental or neuronal dynamics at high frame rates), while maintaining the flexibility and sample geometry of commercially available inverted microscopes (thus additionally allowing wide-field, TIRF, confocal, or 2 photon imaging of samples). CRADA Opportunity: The NIBIB is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize applications of the invention. For collaboration opportunities, please contact Hari Shroff at 301-435-1995 or hari.shroff@nih.gov.

Vaccine to Prevent BK Polyomavirus-associated Kidney and Bladder Infections in Organ Transplant Recipients

Tue, 30 Aug 2011 06:00:00 GMT
Nearly all adults have chronic urinary tract infections with one or more strains of BK polyomavirus (BKV). In healthy persons, the infection is controlled by the immune system and no symptoms are apparent. However, immunosuppressed persons, such as organ transplant recipients, can suffer from bladder disease or kidney disease caused by uncontrolled BKV growth. BKV causes cancer in animals; it is unknown if the same is true in humans. A significant need remains for a means of preventing BKV infection and associated pathologies.

Researchers at the National Cancer Institute, NIH, have developed compositions and therapeutic methods for pre-vaccination of organ transplant recipients against BKV and prognostic methods to identify patients that may benefit from the vaccination. Methods for producing a BKV vaccine against all four known BKV serotypes are in development. CRADA Opportunity: The NCI Center for Cancer Research, Laboratory of Cellular Oncology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

Human Monoclonal Antibodies Cross-reacting to Insulin-like Growth Factors IGF-I and IGF-II as Potential Anti-tumor Agents

Tue, 30 Aug 2011 10:00:00 GMT
The type 1 insulin-like growth factor (IGF) receptor (IGF1R) is over-expressed by many tumors and mediates proliferation, motility, and protection from apoptosis. Agents that inhibit IGF1R expression or function can potentially block tumor growth and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed by multiple tumor types. Previous studies indicate that inhibition of IGF-I, and/or IGF-II binding to its cognizant receptor negatively modulates signal transduction through the IGF pathway and concomitant cell proliferation and growth. Therefore, use of humanized or fully human antibodies against IGFs represents a valid approach to inhibit tumor growth.

The present invention discloses the identification and characterization of a fully human monoclonal antibody designated m708.5 that has been affinity maturated against IGF-I and IGF-II and displays extremely high affinities for IGF-I and IGF-II in the picoM range. The m708.5 antibody potently inhibited signal transduction mediated by the IGF-1R interaction with IGF-I and IGF-II and blocked phosphorylation of IGF-IR and the insulin receptor. Further, this antibody inhibited migration in the MCF-7 breast cancer cell line at the picoM range. Therefore, this antibody can be used to prevent binding of IGF-I and/or IGF-II to its concomitant receptor IGFIR, consequently, modulating diseases such as cancer. CRADA Opportunity: The NCI CCR Nanobiology Program, Protein Interaction Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

TL1A Transgenic Mice for the Study of Inflammatory Bowel Disease (IBD) and Allergic-Type Immune Responses

Tue, 30 Aug 2011 14:00:00 GMT
TL1A is a TNF family cytokine that co-stimulates T-cell proliferation and cytokine production through its interactions with the TNF family receptor DR3. TL1A-DR3 interactions have been shown to be important for the development of autoimmune inflammatory diseases, including inflammatory bowel disease (IBD).

In order to probe the role of TL1A-DR3 interactions in IBD, NIAMS inventors have developed transgenic mice that constitutively express TL1A in T cells or in dendritic cells. These mice spontaneously develop inflammatory small bowel pathology that is IL-13 dependent, and that closely resembles intestinal responses to allergens and to nematode infection.

These mice represent a unique model for the study of IBD, and in particular, the role of IL-13 in the development of this disease. They may also be used as a platform for investigating agents that block TL1A-DR3 interactions and the pathology associated with chronic TL1A expression. CRADA Opportunity: The National Institute of Arthritis and Musculoskeletal and Skin Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize TL1A Transgenic Mice. For collaboration opportunities, please contact Cecilia Pazman at pazmance@mail.nih.gov.

Methods of Treating Giardiasis Using FDA-Approved Compounds

Fri, 12 Aug 2011 18:00:00 GMT
This technology includes a group of at least twenty-nine, diverse, commercially available compounds that are newly identified for activity against Giardia lamblia parasites. At least six of the candidate compounds, Bortezomib, Decitabine, Hydroxocobalamin, Amlexanox, Idarubicin, and Auranofin have preexisting FDA approval for human use for other (non-Giardia) conditions. Another three compounds, Fumagillin, Nitarsone and Carbadox have preexisting approval for veterinary use for non-Giardia conditions. Additional active compounds identified include: Acivicin, Riboflavin butyrate, BTO-1, GW9662, Dinitroph-dfgp, Deserpidine, Tetramethylthiuram disulsulfide, Disulfiram, Mitoxantrone, Ecteinascidin 743, 17-allyaminogeldanamycin, Carboquone and Nocodazole. The anti-Giardial activity of these compounds presents a cost saving opportunity for the rapid development of new, better tolerated treatments for the most prevalent human intestinal parasite infection in the United States and the world. CRADA Opportunity: The NHGRI is seeking stateents of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Novel Compounds for Treatment of Giardiasis. For collaboration opportunities, please contact Claire Driscoll, NHGRI, at cdriscol@mail.nih.gov.

An Automated Method for Precise Measurement of Vertebral Body Height and Intervertebral Disk Height Using Computed Tomography

Fri, 12 Aug 2011 22:00:00 GMT
Vertebral fractures due to osteoporosis result in loss of vertebral height. Degenerative disk disease in the spine results in loss of disk height. Currently, radiography and magnetic resonance imaging are used to assess vertebral and disk height, and measurements are done manually. The present invention offers improved method to measure vertebral and disk heights. The invention provides computer algorithm that substantially automates the task, and uses computed tomography. The advantage of computed tomography over radiography is that of 3D imaging over 2D imaging. Computed tomography's advantage over MRI is better image resolution. The combination of automation and superior imaging capability makes the method substantially more precise than previous ones. This allows better detection of changes in vertebral height and disk height over time, and thus aids in the planning of appropriate medical treatment in cases associated with the loss of vertebral or disc heights, such as in osteoporosis for example. CRADA Opportunity: The National Institute of Arthritis and Musculoskeletal and Skin Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Brian W. Bailey, Ph.D. at bbailey@mail.nih.gov.

Quantitative Measurement of Syndesmophytes in Ankylosing Spondylitis Using Computed Tomography (CT)

Sat, 13 Aug 2011 02:00:00 GMT
Syndesmophyte (abnormal bone) growth in the spine is a hallmark of Ankylosing Spondylitis, a type of inflammatory arthritis. Syndesmophyte growth is currently monitored using semi-quantitative scoring of radiographs, but radiographs consider only a small part of the vertebra, and the method is subject to reader error. Because syndesmophytes grow slowly, radiographs also lack sensitivity. The invention provides a method to measure syndesmophytes using data from computed tomography scans of the lumbar spine. It provides computer algorithm that fully quantitates syndesmophyte volumes in three-dimension space. This method allows precise and accurate measurement of the presence and rate of growth of syndesmophytes over time, which for the first time will permit testing of whether any treatments can slow the progression of this type of spinal arthritis. CRADA Opportunity: The National Institute of Arthritis and Musculoskeletal and Skin Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Brian W. Bailey, Ph.D. at bbailey@mail.nih.gov.

Tumor Markers for Potentially Predicting Outcome of Anti-angiogenesis Therapy

Fri, 05 Aug 2011 06:00:00 GMT
During the past decade, anti-angiogenesis therapy has evolved as a promising approach to the treatment of cancer. However, a significant fraction of patients do not benefit from anti-angiogenesis therapy, either by itself or in combination with chemotherapy. A significant need remains for a means of predicting clinical benefit from anti-angiogenesis therapy.

Researchers at the National Cancer Institute, NIH, have identified tumor cell apoptosis, p53, and HER2 as having potential predictive significance for treatment outcome in breast cancer patients who received anti-angiogenesis therapy in combination with chemotherapy. The researchers have developed a quantitative antibody-based testing method for correlating expression of p53 and HER2 and tumor apoptosis with clinical outcome. These markers can be potentially applied to predict which patients should receive anti-angiogenesis therapy plus chemotherapy. CRADA Opportunity: The National Clinical Target Validation Laboratory, DCTD, NCI, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize p53, tumor apoptosis, and HER2 as markers for anti-angiogenesis therapy. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

An In-Vitro Cell System Useful For Identification of RORgamma Antagonists

Wed, 27 Jul 2011 10:00:00 GMT
The retinoid-related orphan receptors alpha, beta and gamma (RORalpha, beta and gamma , also referred to as NR1F1, 2 and 3, respectively) comprise a distinct subfamily of nuclear receptors. Study of ROR-deficient mice has implicated RORs in the regulation of a number of biological processes and revealed potential roles for these proteins in several pathologies. NIH investigators have developed an in-vitro system using CHO cells stably expressing a TET-On expression vector regulating RORgamma and a RORE-Luciferase reporter. This system allows inducible expression of RORgamma upon addition of doxycycline. Upon its induction RORgamma binds to the RORE in the luciferase reporter plasmid and induces luciferase. This system can be used to identify RORgamma antagonists. This system has been tested successfully in 1536-well plate high throughput analysis. CRADA Opportunity: The NIEHS, Laboratory of Respiratory Biology, Cell Biology Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize retinoid-related orphan receptors (RORs) function in chronic diseases. For collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. at denholme@niehs.nih.gov.

Pertussis Vaccine

Tue, 26 Jul 2011 14:00:00 GMT
Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. This application claims Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. Conjugate-induced antisera were bactericidal against B. pertussis. CRADA Opportunity: The NICHD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize vaccines against pertussis. For collaboration opportunities, please contact Joseph Conrad, III, Ph.D. at jmconrad@mail.nih.gov. Click here to view the NICHD collaborative opportunity announcement.

Layered Electrophoretic Transfer for Analysis of Low or Medium Abundant Proteins in Tissue Samples

Tue, 26 Jul 2011 18:00:00 GMT
The subject invention is a method to selectively process the protein content from a two dimensional sample, such as a tissue section, for more detailed analysis. It is particularly useful for analysis of a subset of proteins from a complex protein mixture. The method employs a layer of polyacrylamide gels and an electric field. Proteins from the sample are transferred and sieved through a stack of polyacrylamide gels of varying concentrations. Thus, it is possible to analyze specific subsets of proteins in the different gel layers and maintain the two dimensional location of the proteins within the original sample. One of the advantages of this technology is that it allows for isolation and subsequent analysis of low abundant or medium abundant proteins by a number of different methodologies such as imaging mass spectrometry. CRADA Opportunity: The Center for Cancer Research, Laboratory of Pathology, Pathogenetics Unit, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize layered electrophoretic transfer (LET). Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Oral Vaccine for Inducing Mucosal Immunity

Thu, 21 Jul 2011 22:00:00 GMT
Available for licensing is a micro/nanoparticle oral vaccine delivery system that specifically targets the large intestine for vaccine deposition and in situ immune activation, with minimal perturbation in the upper part of the gastrointestinal (GI) tract.

Vaccine delivery to the large intestine has been experimentally demonstrated as an effective means for inducing mucosal immunity against infections transmitted through the recto-genital mucosal area such as sexually transmitted disease as well as fungal and parasitic infections. In this system, the vaccine components are encapsulated by nanometer-sized particles to allow optimal uptake once it reaches the lumen and makes contact with the intestinal mucosal surface. To protect from premature degradation and uptake in the upper GI, these particles are coated within micrometer-sized particles. This coating is designed with a pH- and time-dependent release profile that is optimized for vaccine uptake to occur within the large intestine. This particular feature may also make this technology a potential delivery system for recto-colon cancer therapies. CRADA Opportunity: The Center for Cancer Research, Vaccine Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Oral Delivery of a Vaccine to the Large Intestine to Induce Mucosal Immunity. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Monoclonal Antibodies for Rare Diseases

Fri, 22 Jul 2011 02:00:00 GMT
Available for licensing are three monoclonal antibodies (mAb) that bind with high specificity and affinity to the tumor cell surface antigen tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 is expressed in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), two incurable B-cell malignancies that are designated as rare diseases by NIH’s Office of Rare Diseases Research. Therapeutics for rare diseases can qualify for orphan drug status and receive expedited review by the FDA. Currently, there are no therapeutic mAbs that target CLL or MCL but not healthy cells.

Investigators from the National Cancer Institute developed chimeric antibodies that selectively target ROR1 malignant B-cells but not normal B-cells. Additionally, this technology allows for mAb derivatives with potentially higher pharmacokinetic and/or pharmacodynamic activity, including humanized mAb in an IgG and IgM format, antibody-drug conjugates, immunotoxins, and bispecific antibodies. These three mAbs have been characterized in vitro for mediating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, apoptosis, and internalization. Results show that these mAbs bind with high specificity and affinity to three different epitopes on human ROR1, and ROR1-expressing primary CLL cells from untreated CLL patients and MCL cell lines. Moreover, as these antibodies selectively target ROR1, they can also be used to diagnose B-cell malignancies. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Experimental Transplantation and Immunology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-ROR1 monoclonal antibodies and their derivatives. Please contact Dr. Christoph Rader at (301) 451-2235 or raderc@mail.nih.gov for more information.

An Antibody Specific for the Ubl4A Protein

Thu, 21 Jul 2011 06:00:00 GMT
The antibody developed against the Ubl4A protein is available for licensing. Ubl4A is involved in the proper targeting of tail-anchored proteins to membranes by acting as a chaperone to prevent inappropriate interactions or aggregation. Alterations in membrane insertion or protein degradation may be related to Ubl4a in certain disease states making Ubl4a an attractive biomarker for the study of disease development or as a tool for the development of assays for disease detection. CRADA Opportunity: The NICHD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Ubl4A assay detection for disease diagnostics. Please contact Charlotte McGuinness at 301-435-3130 or mcguinnc@mail.nih.gov for more information.

Immunocompetent Mouse Model for Tracking Cancer Progression

Fri, 01 Jul 2011 10:00:00 GMT
The technology is a transgenic mouse model tolerized to firefly Luciferase (ffLuc)- and enhanced green fluorescent protein (eGFP)-labeled tissue whilst maintaining normal immune function. Luc and eGFP are the most frequently used bioimaging markers to track cancer progression in pre-clinical mouse models. As these markers are immunogenic, their reporter activity becomes diminished over time and so their use has largely been limited to immunodeficient mice. However, immune function is crucial for tumor development and progression, making the use of immunocompetent mice more desirable.

The immunocompetent mouse model described in this invention was generated using the rat growth hormone gene promoter (rGH) to target ffLuc-eGFP fusion gene expression to the pituitary gland, restricting any resulting interfering reporter signal within the head. This allows the tracking of cancer progression throughout the body, where the reporter activity of introduced ffLuc/eGFP-labeled tumors is maintained, despite normal immune function. These immunocompetent rGH-ffLuc-eGFP transgenic mice can be used as hosts in cancer models, allowing long-term in vivo monitoring of the progression of ffLuc/eGFP-labeled tumor cells in the body, which may lead to more clinically relevant insights into cancer progression, metastases and response to therapies. CRADA Opportunity: The National Cancer Institute Center for Cancer Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immunocompetent rGH-ffLuc-eGFP transgenic mice. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Breakthrough Immunotherapy for Brain Cancer

Fri, 01 Jul 2011 14:00:00 GMT
Chimeric antigen receptors (CARs) with high affinity for the epidermal growth factor receptor variant III (EGFRvIII) for use as an immunotherapy for glioblastoma and other cancers. CARs are hybrid proteins consisting of the portion of an antibody that recognizes a cancer antigen, in this case human monoclonal antibody 139. This Mab recognizes EGFRvIII, fused to protein signaling domains that serve to activate the CAR-expressing cell. Human cells that express CARs, most notably T cells, can recognize specific tumor antigens in an MHC-unrestricted manner with high reactivity and mediate an immune response that promotes robust tumor cell elimination.

EGFRvIII is a rare antigen in that is highly expressed by tumor cells, but not expressed by other cells in the body. This cancer antigen is expressed on nearly 50% of glioblastoma multiforme tumor cells and other tumor types, such as other nervous system and head and neck cancers. There exist very few, if any, effective treatments for glioblastoma multiforme.

These CARs are expected to combine high affinity recognition of EGFRvIII provided by the antibody portion with the target cell killing activity of cytotoxic T cells. Infusion of these EGFRvIII-specific CARs into patients could prove to be a powerful new immunotherapeutic tool for treating brain cancers. CRADA Opportunity: The National Cancer Institute, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cell-based immunotherapies targeting EGFRvIII expressing cancers. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Inhibitors of Human Apurinic/apyrimidinic Endonuclease 1 (APE1), an Anticancer Drug Target

Fri, 01 Jul 2011 18:00:00 GMT
APE1 is the primary mammalian enzyme responsible for the removal of abasic (AP sites) in DNA and functions as part of the base excision DNA repair pathway (BER). BER is instrumental in the repair of DNA damage caused by DNA alkylating agents (e.g. many cancer chemotherapeutics). APE1 has been shown to be overexpressed in cancer cells. It has been postulated that APE1 would be an attractive target in anti-cancer treatment paradigms; preclinical and clinical data confirm that APE1 is a valid anticancer drug target.

To date, only one APE1 small molecule inhibitor has progressed to clinical trials (methoxyamine hydrochloride), and this compound inhibits a wide range of repair processes, which could result in undesired side-effects. The NIH inventors now report the discovery of a novel APE1 small molecule inhibitor, which exhibits potent in vitro activity, potentiates the cytotoxicity of DNA damaging agents (alkylators methylmethane sulfonate and Temozolomide), results in the accumulation of AP sites, and has favorable pharmacokinetic properties. The inventors plan to carry out further studies in mouse tumor xenograft models. CRADA Opportunity: The NIH Center for Translational Therapeutics, NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the above technology. Please contact Lili Portilla, Acting Director of Technology Transfer and Partnerships, NCTT at Lilip@nih.gov for more information.

Mouse Model and Derived Cells That Hypersecrete Leukemia Inhibitory Factor (LIF)

Fri, 01 Jul 2011 22:00:00 GMT
Embryonic stem cells (ESCs) are pluripotent cells that can be cultured indefinitely, and maintain their capability to differentiate into all cell lineages. To maintain these cells as well as various types of related induced stem cells and progenitor cells in culture, Mouse Embryonic Fibroblasts (MEFs) are routinely used as feeder cells, largely to serve as a source of Leukemia Inhibitory Factor (LIF). ESCs can also be cultured without feeders if the medium is supplemented with recombinant LIF and other factors. However, these methods of culturing ESCs suffer from certain drawbacks, such as limited proliferation capacity and variability of primary MEFs. Therefore, finding improved conditions that maintain ESC pluripotency is an area of great interest.

Scientists at NIEHS have now developed a knock-in (KI) mouse model in which LIF is overproduced from its endogenous locus because of increased stability of its mRNA. MEFs and presumably other cells derived from the homozygous mice hypersecrete LIF protein; lesser degrees of overexpression would be expected from heterozygous mice. These mice can be used to study LIF function, including how LIF contributes to various physiological and pathological states. Cells derived from these mice can be used to culture ESCs, as well as other progenitor cells. Cells or genetic material derived from these mice can also be used as sources of LIF for isolation and purification. CRADA Opportunity: The NIEHS Laboratory of Signal Transduction is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these mice or other strains derived from them, or cells or other reagents derived from them. Please contact Dr. Elizabeth Denholm (denholme@niehs.nih.gov) in the NIEHS Office of Technology Transfer, or the Inventor Dr. Perry Blackshear (black009@niehs.nih.gov) for more information.

System for Correction of MRI Head Motion

Mon, 27 Jun 2011 02:00:00 GMT
Motion artifacts continue to be a significant problem in MRI of human brain. Prospective motion correction based on external tracking systems has been proposed to ameliorate this issue. However, the calibration of these systems is very complicated and time consuming, as it requires a camera system calibration as well as a calibration between camera and MRI system using dedicated phantoms. An alternative motion correction method for MRI that does not require calibration and can work with just a single video camera has been developed and is available for licensing. This technology can be broadly applied in MRI to account for motion artifacts in order to improve acquisition time and provide enhanced resolution. This technique will provide a needed method to obtain reliable MRI scans for uncooperative patients (children, seizure patients, etc.) without the need and expense of multiple scans. CRADA Opportunity: The National Institute of Neurological Disorders and Stroke - Advanced MRI Section - Laboratory of Functional and Molecular Imaging is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MRI methods to improve data collection by improved homogeneity, resolution, etc. Please contact Dr. Melissa Maderia at 301-451-3943 or maderiam@mail.nih.gov for more information.

Antibody and Immunotoxin Treatments for Mesothelin-expressing Cancers

Fri, 17 Jun 2011 06:00:00 GMT
Mesothelin is a cell surface protein that is highly expressed in aggressive cancers such as malignant mesothelioma, ovarian cancer and pancreatic cancer. As a result, mesothelin is an excellent candidate for tumor targeted immunotherapeutics. However, the antibodies against mesothelin that are available for clinical trials are of murine origin. These antibodies have the potential to elicit immune responses in patients, which may adversely affect the ability to provide patients with repeated doses. Thus, the clinical application of the antibodies may be limited.

In order to address the issue of immunogenicity in patients, NIH inventors have generated anti-mesothelin antibody variable fragments (Fv) of human origin. These antibody fragments (HN1 and HN2) have the ability to efficiently recognize mesothelin on the surface of numerous cancer cells. As a result, these antibody fragments represent an attractive therapeutic alternative to the murine anti-mesothelin antibodies currently being tested in clinical trials. CRADA Opportunity: The National Cancer Institute Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antibody-based treatments of mesothelin-expressing cancers. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Increased Therapeutic Effectiveness of Immunotoxins Through the Use of Less Immunogenic Toxin Domains

Wed, 15 Jun 2011 10:00:00 GMT
Targeted toxins (e.g., immunotoxins) are therapeutics that have at least two important components: (1) a toxin domain that is capable of killing cells and (2) a targeting domain that is capable of selectively localizing the toxic domain to only those cells which should be killed. By selecting a targeting domain that binds only to certain diseased cells (e.g., a cell which only expresses a cell surface receptor when in a diseased state), targeted toxins can kill the diseased cells while allowing healthy, essential cells to survive. As a result, patients receiving a targeted toxin are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy.

A particular toxin that has been used in targeted toxins is Pseudomonas exotoxin A (PE). The effectiveness of PE-containing targeted toxins has been demonstrated against various forms of cancer, including hairy cell leukemia (HCL) and pediatric acute lymphocytic leukemia (pALL). Although early variations these targeted toxins have demonstrated efficacy upon first administration, the continued administration of a targeted toxin often leads to a reduced patient response. The primary cause of the reduced response is the formation of neutralizing antibodies against PE by the patient.

Several variations of PE have been created to reduce the immunogenicity of PE as a means of increasing the therapeutic effectiveness of targeted toxins through multiple rounds of drug administration. This technology involves the identification of two important B-cell epitopes on PE, and the elimination of those epitopes by mutation. These new PE variants retain a sufficient cell killing activity while increasing their therapeutic effectiveness toward patients that receive multiple administrations. By further combining these new mutations with previously identified modifications that also improve the efficacy of PE-based targeted toxins, it may be possible to treat any disease characterized by cells that express a particular cell surface receptor when in a disease state. CRADA Opportunity: The National Cancer Institute, Molecular Biology Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Mouse Xenograft Model for Mesothelioma

Wed, 15 Jun 2011 14:00:00 GMT
Malignant mesothelioma is a cancer that presents itself in the protective lining of several organs (e.g., lung, heart, testis, etc.). The primary cause for mesothelioma is direct or indirect exposure to asbestos, although the disease can present without any prior exposure. Mesothelioma is relatively rare, but the prognosis for patients is poor, indicating a need to better understand and treat the disease. Current treatments often involve chemotherapy and radiation therapy, although recent studies have employed the use of therapeutic antibodies and antibody-targeted toxins.

This invention involves the creation of a new mouse model for mesothelioma. By creating xenografts with mesothelioma cells that express GFP-Luciferase fusion proteins, the xenografts can be detected to a high degree of sensitivity, and monitored for several months following implantation. The high level of detection sensitivity improves the ability to monitor disease progression in response to therapeutic candidates, thereby allowing more efficient drug screening and evaluation. This has already been demonstrated by using the mouse to evaluate an anti-mesothelioma immunotoxin known as SS1P, a drug candidate that is currently being evaluated for clinical effectiveness. CRADA Opportunity: The Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize monoclonal antibodies and immunoconjugates targeting malignant mesotheliomas. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Human Monoclonal Antibodies to Glypican-3 Protein and Heparin Sulfate for Treatment of Cancer

Wed, 15 Jun 2011 18:00:00 GMT
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and is among the more deadly cancers in the world due to its late detection and poor prognosis. No effective treatment is available for liver cancer therapy.

Glypican-3 (GPC3) is a cell surface protein that is preferentially expressed on HCC cells, making it an attractive potential target for developing a therapeutic. This invention concerns human monoclonal antibodies against GPC3 and their use for the treatment of GPC3-expressing cancers such as HCC.

Specifically, the inventors have generated two distinct human monoclonal antibodies to GPC3. The first antibody (HN3) binds to a conformational epitope on the cell surface domain of GPC3. The second antibody (HS20) binds specifically to heparan sulfate chains on GPC3. These antibodies can inhibit the growth of HCC cells, thereby decreasing the ability of tumors to grow and metastasize. Furthermore, by using the antibodies to target a toxic moiety to only those cells that express GPC3, cancer cells can be eliminated while allowing healthy, essential cells to remain unharmed. Thus, monoclonal antibodies to GPC3 (and corresponding immunotoxins) represent a novel therapeutic candidate for treatment of HCC, as well as other cancers associated with the differential expression of GPC3. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel antibody or antibody-drug conjugate therapies for the treatment of liver cancer. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.

MicroRNA-205 for the Treatment and Diagnosis of Parkinson Disease

Wed, 15 Jun 2011 22:00:00 GMT
Parkinson disease (PD) is a devastating neurodegenerative movement disorder, pathologically characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of intracytoplasmic inclusions named Lewy bodies and Lewy neurites (Schapira, Baillieres Clin. Neurol. 6:15-36, 1997). Increasing numbers of genes have been identified as a genetic cause of PD (Hardy et al., Ann. Neurol. 60:389-398, 2006), for example, multiple missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene were recently found to be associated with an autosomal dominant form of familial PD (Paisan-Ruiz et al., Neuron 44:595-600, 2004; Zimprich et al., Neuron 44:601-607, 2004; Zabetian et al., Neurology 65:741-744, 2005). Recent genome-wide association studies (GWAS) also revealed LRRK2, together with SNCA (encoding alpha-syn) and PARK16, as shared risk loci for PD (Simon-Sanchez et al., Nat. Genet. 41:1308-1312, 2009; Satake et al., Nat. Genet. 41:1303-1307, 2009), indicating a potential contribution of normal LRRK2 protein to the etiology of sporadic PD cases.

Micro-RNAs (miRNAs or miRs) are evolutionarily conserved small non-protein coding transcripts that bind to partially complementary binding sites in the 3’ untranslated region (3’-UTR) of target messenger RNAs (mRNAs) and control the translation of their target mRNAs at the post-transcriptional level (Bartel, Cell 116:281-297, 2004). Several miRNAs have been associated with neurodegenerative disease as well as synaptic plasticity, memory formation and developmental cell fate decisions in the nervous system (Hebert and De Strooper, Trends Neurosci. 32:199-206, 2009; Kosik, Nat. Rev. Neurosci. 7:911-920, 2006).

NIH inventors have recently discovered that LRRK2 protein expression is significantly increased in the brain of PD patients, while expression of miR-205 is specifically down-regulated in the same patients. Also, the NIH inventors have discovered that the expression levels of LRRK2 and miR-205 are dynamically regulated and reversely correlated in multiple brain regions and at different ages in mouse brains, indicating that miR-205 plays a regulatory role in LRRK2 protein expression.

Based on these novel findings, the present technology provides for novel methods of treatment of patients suffering from PD disease by modulating the amount of miR-205 in patients by administration of a miR-205 gene product, a vector encoding a miR-205 gene product or an agent that increases expression of miR-205. The present technology also provides for methods of determining the effectiveness of different candidate drugs for the treatment of PD, methods of diagnosing PD, or having an increased susceptibility to developing PD, and an in vitro process for identifying a therapeutic agent for the treatment of PD. CRADA Opportunity: The National Institute on Aging, Transgenics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize microRNA-205 or other reagents for the treatment and diagnosis of Parkinson Disease. Please contact Nicole Guyton, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information. Click here to view the NIA collaborative opportunity announcement.

Liver Segmental Anatomy and Analysis from Vessel and Tumor Segmentation

Thu, 16 Jun 2011 02:00:00 GMT
The invention is a novel graph-based method for the automated segmentation of tumors and major intra-hepatic blood vessels and identification of the liver anatomical segments. The method allows visualization and risk analysis for interventional planning involving the liver. The method avoids the shortcomings of the traditional graph cuts or intensity-based segmentation methods by including multi-phase enhancement modeling and shape likelihoods. The segmented vessels can be correctly classified into right, middle and left hepatic, and right and left portal veins using a hybrid process that incorporates anatomical information and competitive region growing. Tumors can be detected and segmented using their differential enhancement and shape with accuracy comparable to the reports from the Medical Image Computing and Computer Assisted Intervention (MICCAI) liver tumor segmentation competition. Furthermore, a vessel tracker allowed fitting planes to the major hepatic vasculature and identifying the liver segments according to the Couinaud atlas. The automated method can be used in conjunction with manual and automatic liver segmentations to perform enhanced visualization for diagnosis and planning of interventions. CRADA Opportunity: The NIH Clinical Center, Department of Radiology and Imaging Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize techniques for the enhanced visualization, diagnosis and image-based interventions of the liver. Please contact Ken Rose, Ph.D. at 301-435-3132 or rosek@mail.nih.gov for more information. Click here to view the NIH Clinical Center collaborative opportunity announcement.

A System for Delivering Embolic Materials Endovascularly to Patients

Wed, 15 Jun 2011 06:00:00 GMT
The Public Health Service seeks commercial entities interested in licensing patent rights that pertain to a system for delivering embolic materials endovascularly to patients. The system includes a smart catheter that provides quantitative feedback to a physician during embolotherapy. This includes a detecting portion for measuring flow velocity (e.g., Doppler tip), amount of reflux, and amount of embolic particles (e.g., embolization beads) delivered by the catheter. A graphical user interface displays the measured information in real-time. CRADA Opportunity: The NIH Clinical Center, Radiology and Imaging Sciences Department, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a catheter for quantitative feedback during embolotherapy. Please contact Ken Rose, Ph.D. at 301-435-3132 or rosek@mail.nih.gov for more information. Click here to view the NIH Clinical Center collaborative opportunity announcement.

Oligonucleotide Compounds that Enhance Immunity to Cancer and Reduce Autoimmunity

Wed, 15 Jun 2011 10:00:00 GMT
Suppressive cells, including macrophages and other myeloid-derived suppressor cells, regulatory T cells, and dendritic cells (DCs), have been attributed to tumor growth. DCs in particular are known to be associated with the induction of T cell tolerance in cancer, but molecular mechanisms that control DC dysfunction are complex and a better understanding of DC mechanisms in tumors is needed. Recently FOXO3, originally identified as a tumor suppressor, was associated with DC dysfunction. Additionally, therapeutics targeting FOXO3 are known to be effective at killing many tumors types, synergize with traditional therapies, and show efficacy against tumors that are otherwise resistant to conventional treatments.

The researchers at the NIH have demonstrated for the first time that FOXO3 expression by DC coincides with expression of suppressive genes that negatively regulate T cell function. They have also demonstrated that silencing FOXO3 simultaneously changes DC function, eliminating tolerogenicity and enhancing their immunostimulatory capacity. Specifically, the inventors have developed siRNAs or oligonucleotides that enhance an immune response and neutralize the activity of FOXO3 in DCs by converting suppressive cells into immunostimulatory cells. This novel approach could be applied to cancer vaccines, where dendritic cells could be treated with these small molecules prior to use in clinical therapies. Alternatively, small molecules that stimulate FOXO3 expression could be used for inducing immune suppression for autoimmune diseases like type I diabetes or multiple sclerosis. CRADA Opportunity: The National Cancer Institute Cancer and Inflammation Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize agents that both block FOXO3 function and enforce FOXO3 expression. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Novel Small Molecule Inhibitors for the Treatment of Huntington’s Disease

Fri, 03 Jun 2011 14:00:00 GMT
This technology is a collection of small molecules screened for their ability to prevent or reduce the cytotoxic effects of the protein, Huntingtin. Huntington's disease is a neurodegenerative disorder due to a dominantly acting expansion of a CAG trinucleotide repeat in exon 1 of the Huntington (HTT) gene resulting in production of the altered (mutant) protein Huntingtin, which has a long chain of polyglutamine (poly Q) attached to the exon 1 encoded protein sequence. Clinical and statistical analyses have shown that an increased number of poly Q repetition correlates with the probability of developing the disease, with 36 to 40 being the accepted cut off number for developing the disorder with high probability. It is known that poly Q repetitions impact the physical properties of Huntingtin and cause it to produce aggregates that precipitate and form inclusion bodies, which are toxic to the neuronal cells. The compounds of this invention have been screened multiply in a neuronal cell model of Huntington’s disease containing an HTT with an expanded repeat in exon 1 of 103 Qs for their ability to inhibit cytotoxicity and protein aggregation. CRADA Opportunity: The National Center for Translational Therapeutics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology further. Please contact Ms. Lili Portilla at Lilip@nih.gov for more information.

Synergistic Combination Agent (Ceramide and Vinca Alkaloids) for Cancer Therapy

Fri, 03 Jun 2011 18:00:00 GMT
Work by the Nanotechnology Characterization Laboratory (NCL), a joint initiative of NCI, NIST, and the FDA, has led to the discovery of a novel combination chemotherapy. This combination is shown to have synergistic effects on cytotoxicity to cancer cells in vitro, and to cause a substantial decrease in tumor growth in preclinical tumor models in vivo. Combination therapy using these agents may enhance the response rate of different cancers to these drugs and may significantly reduce side effects by permitting a lower therapeutic dose to be administered.

The instant invention relates to a novel combination of ceramide and vinca alkaloids, which synergistically decrease cancer cell growth without increasing the toxicity profile compared to the individual drugs. The drug combination has been rigorously evaluated in both in vitro and in vivo models of cancer, and a dose range-finding toxicology study has been conducted in rodents.

This combination induces cell death via a novel mechanism (induction of autophagy with simultaneous blockade of autophagy flux). This mechanism appears to impart selectivity of the therapy to cancer cells.

Available for licensing are methods to use the combination therapy for cancer treatment. CRADA Opportunity: The SAIC Frederick, Nanotechnology Characterization Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a ceramide and vinca alkaloid combination therapy for treatment of cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

HIF1alpha-Targeted Therapy for Diabetes and Obesity

Fri, 03 Jun 2011 22:00:00 GMT
This technology describes the use of hypoxia inducible factor 1 alpha (HIF1alpha) inhibitors for the reduction of body weight and treatment of diabetes.

In obesity, the rapid expansion of adipose tissue outpaces the oxygen supply, resulting in hypoxia. HIF1alpha, a transcription factor that plays an essential role in cellular and systemic responses to low oxygen levels, is activated in these tissues, and causes inflammation that has been linked to insulin resistance and other metabolic dysfunction.

To examine the role of hypoxia in obesity and insulin resistance, investigators at the National Cancer Institute disrupted the HIF1alpha gene (or its dimerization partner, the HIF1beta) in the adipose tissue of transgenic mice, and found that these mice were protected from obesity and insulin resistance when fed a high-fat (western) diet. In further experiments, administration of an HIF1alpha inhibitor to wild-type mice achieved similar reductions in fat mass and insulin resistance, as well as other indicators of metabolic disease. Thus, HIF1alpha inhibitors represent promising new leads for obesity and diabetes therapeutics. CRADA Opportunity: The Center for Cancer Research, Laboratory of Metabolism (LM), is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HIF1alpha inhibitors that can be used for the treatment of obesity and type 2 diabetes. The LM will be willing to collaborate with parties to evaluate potential inhibitors using the HIF1alpha adipose-specific knockout mice. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

X-Clometer: Optimizing Portable Radiography

Sat, 04 Jun 2011 02:00:00 GMT
The technology offered for licensing and commercial development relates to a method and apparatus that can significantly improve the diagnostic performance of portable chest (CXR) and abdominal x-rays. This device quantifies angulation of a patient to provide for a better comparison of day-to-day improvement.

The portable CXR is one of the most commonly requested diagnostic medical tests around the world. They are performed nearly daily on some of the sickest patients in hospitals. Paradoxically, it is well documented that portable radiography of the chest is inconsistent and often inadequate.

An upright projection best evaluates effusions, rules out free air, or detects air-fluid levels. Optimally, the images are obtained at similar angles each day, even if not erect, to allow accurate comparisons and assessment of change. It is well documented that portable radiography of the chest is inconsistent and often inadequate. To achieve optimal quality of the exam the technologist attempts the most upright projection; balanced with patient condition and ability to achieve this often impossible task. CRADA Opportunity: The NIH Clinical Center, Radiology and Imaging Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize X-Clometer. Please contact Ken Rose, Ph.D. at 301-435-3132 or rosek@mail.nih.gov for more information. Click here to view the NIH Clinical Center collaborative opportunity announcement.

Methods and Devices for Transcatheter Cerclage Annuloplasty

Wed, 25 May 2011 06:00:00 GMT
The invention relates to techniques and devices for cardiovascular valve repair, particularly annuloplasty techniques and devices in which tensioning elements are positioned to treat regurgitation of the mitral valve or tricuspid valve. More specifically, the technology pertains to a new device for myocardial septal traversal ("cerclage reentry") that also serves to capture (ensnare) and externalize the traversing guidewire. The focus of the invention is to avoid a phenomenon in cardiac surgery known as "trabecular entrapment." The device features an expandable and collapsible mesh deployed in the right ventricle to simplify capture of a reentering guidewire during transcatheter cerclage annuloplasty. The wire mesh exerts pressure against trabecular-papillary elements of the tricuspid valve to displace them against the right ventricular septal wall. By abutting the right ventricular reentry site of the cercalge guidewire, trabecular entrapment is avoided. The device comprises a shaft having a distal loop which provides a target in the interventrical myocardial septum through which a catheter-delivered tensioning system is guided. The loop ensnares the catheter-delivered tensioning system as it reenters the right ventricle or right atrium. The expandable and collapsible mesh is disposed within the right ventricle such that the catheter-delivered tensioning system is directed from the ventricular septum into the right ventricular cavity through only a suitable opening in the mesh and such that the catheter delivered tensioning system is captured or ensnared within the mesh opening. CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Peg Koelble at koelblep@nhlbi.nih.gov for more information.

Thrombolytic Temperature-Sensitive Liposomes

Wed, 25 May 2011 10:00:00 GMT
The subject technology discloses a novel method for inducing targeted thrombolysis in blood vessels. In this technology, a thrombolytic agent is encapsulated within temperature-sensitive liposomes. This composition is administered into the patient’s blood circulation. Certain clots and vulnerable atherosclerotic processes elicit an endogenous heat that facilitates local thrombolytic drug release. The thermosensitive liposome can also be exogenously heated to at least its phase transition temperature to induce the release the thrombolytic agent from the liposome at the thrombus for targeted thrombolysis. The temperature for activated release can be varied, depending on the specific composition of the liposome. CRADA Opportunity: The NIH Clinical Center, Interventional Radiology Section & Center for Interventional Oncology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this novel approach to thrombolysis. Please contact Ken Rose, Ph.D. at 301-435-3132 or rosek@mail.nih.gov for more information. Click here to view the NIH Clinical Center collaborative opportunity announcement.

Peptide Therapeutics for Cardiac Failure

Fri, 20 May 2011 14:00:00 GMT
Available for licensing are therapeutic peptides that induce heart contractions without affecting blood pressure during cardiac failure. During cardiac failure, the heart suffers a decrease in contraction force, which weakens the heart’s ability to deliver blood. Interestingly, the failing heart also retains an ability to increase its contraction force. This represents the theoretical basis for treatment of heart failure with positive inotropic agents, which increase heart contractility. Currently available positive inotropic agents include catecholamines such as epinephrine, Milrinone, and beta-receptor agonists. However, these treatments demonstrate negative side effects including increased blood pressure as well as heart attack.

Investigators at the Eunice Kennedy Shriver National Institute of Child Health and Human Development have developed therapeutic peptides designated as Serpinin and its derivative pGlu-Serpinin. These peptides act via a signaling pathway independent from the classical receptor-mediated adrenergic pathway and as a result, they can increase heart contractility without affecting blood pressure. These peptides represent a novel pharmacological approach in the treatment of cardiac failure. CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Cellular Neurobiology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of serpinin and pyroglu-serpinin in treatment of heart failure. Please contact Joseph Conrad at 301-435-3107 or jmconrad@mail.nih.gov for more information. Click here to view the NICHD collaborative opportunity announcement.

Vaccines for Protection Against Mucosatropic Infections

Fri, 20 May 2011 18:00:00 GMT
The invention offered for licensing and commercial development relates to the field of Vaccines. More specifically, the invention describes novel compositions, strategy and methods that can effectively induce local mucosal immune response (e.g. in a female genital tract that is infected with a mucosatropic pathogen), as well as systemic immune response. The method comprises administrating to the treated subject at least two (2) immunogenic compositions in a prime-boost regimen, each comprising an effective amount of an immunogen derived from the pathogen. The first composition is administered to the epithelial surface of the subject in combination with one or more agents or treatment to disrupt the epithelial surface (e.g.nonoxobol-9 or depot medroxyprogesterone acetate). The second immunogenic composition is administered systemically. The first composition is typically a papillomavirus pseudovirion (PsV) comprising a polynucleotide that encodes proteins on the mucosatropic pathogen. The PsV has shown to confer tropism for the basal epithelium and is uniquely capable of eliciting strong immune response at this environment. The immunogenic composition that is administered systemically is typically selected from one of the following groups: (a) a live attenuated virus (e.g. poxivirus) expressing a protein or proteins of the infecting pathogen, (b) a DNA vector encoding proteins of the pathogen, or (c) an immunogenic polypeptide from the pathogen. CRADA Opportunity: The Center for Cancer Research, Vaccine Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Vaccines for Protection Against Mucosatropic Infections. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

A Novel Strategy for Development of an Effective HIV/AIDS Vaccine

Fri, 29 Apr 2011 22:00:00 GMT
The invention offered for licensing and commercial development relates to the field of HIV/AIDS Vaccines. More specifically, the invention describes a novel strategy that can be useful in effective vaccination and treatment of HIV/AIDS infected persons. In this strategy (called ‘trigger-and-neutralize’ strategy) the infected subject is primed with HIV trimeric gp 120 immunogen to induce the production of CD4i (CD4-induced) antibodies. The patient is then treated with a compound that stabilizes the ‘open’ conformation of the gp120 of the HIV virus, at which conformation the gp120 epitope is better exposed and effectively neutralized by the CD4i antibodies. CRADA Opportunity: The Center for Cancer Research, NCI/NIH is seeking statements of capability or interest from parties interested in collaborative research to further develop, produce, evaluate, or commercialize trimeric gp120 immunogens. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Novel Inhibitors of Thymic Stromal Lymphopoietin (TSLP) for Cancer Therapy

Fri, 15 Apr 2011 02:00:00 GMT

Compositions and methods of using antagonists of thymic stromal lymphopoietin (TSLP) to prevent cancer progression and metastasis.

TSLP, an inflammatory cytokine that is often associated with the induction of allergic responses in the lungs, is also expressed in cancers regulating metastasis. The cancer-promoting activity of TSLP primarily requires signaling through a receptor on CD4+ T-cells, promoting immune responses and production of immunosuppressive factors such as IL-10 and IL-13. Expression of TSLP may be a useful prognostic marker and inhibitors of TSLP could have therapeutic potential. Inactivation of TSLP expression or its receptor signaling was able to effectively diminish cancer progression and metastasis in knock-out mice.
CRADA Opportunity: The National Institute on Aging, Immunotherapeutics Unit, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize clinical application of TSLP in cancers. Please contact Nicole Guyton, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Altered miRNA Expression as Diagnostics and Therapeutics for Adrenocortical Carcinomas

Thu, 14 Apr 2011 06:00:00 GMT

This technology describes that altered human miRNA expression such as miRNA-483 and miRNA 100 can accurately predict if a patient's adrenal cortex tumor is benign or malignant. Adrenocortical carcinomas (ACC) are rare but aggressive cancers and typically have a poor prognosis. Currently, there are limited options for molecular diagnosis to distinguish malignant tumors from benign tumors of this type. As a result there are few treatment strategies for ACC.

Preliminary results suggest that altering the expression of this miRNA in ACC cells can effect cancer cell growth. Therefore, inhibiting a miRNA may serve as a therapeutic option for ACC.
CRADA Opportunity: The Center for Cancer Research, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of diagnostic miRNAs and to target these miRNAs for treatment. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

NAG-1 Transgenic Mouse Model

Thu, 14 Apr 2011 10:00:00 GMT
The nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) encodes a protein that has anti-inflammatory, proapoptotic, and antitumor properties. It plays a pivotal role in antitumorigenesis induced by chemopreventive compounds. Transgenic mice expressing human NAG-1 have been developed by the NIH investigator and collaborator.

The NAG-1 transgenic mice are shown to develop few tumors in response to carcinogenic stimuli than wild type mice. They are also leaner with less fat than their wild type counterparts. As such, these mice can be used to investigate the development of cancers, and they could be of value in studying obesity and the relationship to cancer risk, and inflammation. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Elizabeth M. Denholm, NIEHS Office of Technology Transfer, denholme@niehs.nih.gov, 919-541-0981, for more information.

Diagnostic and Prognostic Serum Biomarkers for Cancer Patients Treated with Cancer Vaccines

Tue, 29 Mar 2011 14:00:00 GMT
Although antibodies are a critical element of the immune response, the role of antibody responses in cancer vaccines is still unknown. Carbohydrate antigens, which are directly or indirectly involved in most types of cancer vaccines, are a class of antigens has been largely understudied but play a significant role in the immune response of cancer vaccines.

This invention involves the identification of serum biomarkers for cancer that target carbohydrate antigens. The biomarkers are specific sub-populations of serum antibodies present in the serum of patients that bind to various glycan and/or glycoprotein antigens, such as the Forssman antigen.

The biomarkers are useful for a) predicting a patient’s immune responses to a cancer vaccine, b) measuring the efficacy of a cancer vaccine, and c) determining the prognosis and long-term survival of cancer patients. CRADA Opportunity: The Center for Cancer Research, Chemical Biology Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-glycan serum antibodies as biomarkers for cancer or HIV vaccines and/or as prognostic biomarkers. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Superparamagnetic Nanocomplexes and Their Use as Contrast Agents in MRI

Tue, 29 Mar 2011 18:00:00 GMT
The invention offered for licensing and commercial development relates to the fields of cell therapy and tracking of such therapy by magnetic resonance imaging. More specifically the technology describes novel superparamagnetic magnetic resonance contrast agents, methods of making the agents, and methods of labeling cells with the contrast agents and imaging the labeled cells using magnetic resonance.

The self assembled agents are composed of three (3) components: Superparamagnetic iron oxide nanoparticle (e.g. F₃O₄), associated with a carbohydrate coating (e.g., a polycation (e.g., Protamine Sulfate); and a polycation (e.g., glycosaminoglycan:Heparin). Self-assembling superparamagnetic nanocomplexes made from simple commercially available chemicals such as Heparin sulfate (H), Protamine sulfate (P), and Ferumoxytol nanocomplexes (HPF nanocomplexes) can effectively label stem cells, immune cells, tumor cells, or any other therapeutically engineered cells for cellular MRI. Biological cells can be labeled with the nanocomplexes by contacting cells under conditions sufficient to produce the nanocomplexes, or by contacting the cells with pre-assembled nanocomplexes. The labeled biological cells can be transplanted into an individual, imaged by MRI and the migration pattern and/or cellular distribution pattern of the labeled biological cells in the subject can then be detected. This technique will readily facilitate the tracking of the therapeutic cells, and thus render cell-based therapy and/or tissue repair more precise, accurate and effective. CRADA Opportunity: The Clinical Center, Frank Laboratory, Radiology and Imaging Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Joseph A. Frank MS MD at 301-402-4314 or jafrank@helix.nih.gov for more information. Click here to view the Clinical Center collaborative opportunity announcement.

Modulation of Leucine-rich Repeats and Calponin Homology Domain-containing Protein 4 (Lrch4) Activity for Therapeutic Applications

Tue, 29 Mar 2011 22:00:00 GMT
NIH Inventors have recently discovered a novel Leucine-rich repeat and calponin homology domain-containing protein 4 (Lrch4) in a proteomic screen of the plasma membrane of lipopolysaccharide (LPS)-exposed macrophages. Expression data by RT-PCR revealed that all Lrch family members (1-4) are expressed in macrophages, but only Lrch4 was recruited into lipid rafts (signaling microdomains of the plasma membrane) by LPS. Lrch4 is the most highly expressed Lrch family member in mouse tissues. It is a predicted single-spanning transmembrane protein that is encoded by the Lrch4 gene in humans. The Lrch4 ectodomain is predicted to have a series of leucine-rich repeats, the motifs by which Toll like Receptors (TLR) are thought to bind microbial ligands. The human form of Lrch4 is 83% identical to murine Lrch4 and is predicted to have 680 amino acids and a molecular weight of 73 kDa.

NIH inventors have shown that Lrch4 is expressed on the plasma membrane of macrophages. They have determined that Lrch4 regulates pro-inflammatory signals (NF-kappaB activation, cytokine induction) emanating from all TLRs tested, and also regulates ligand-independent signals from MyD88. Further, LPS-induced p38, JNK, and NFkappaB activation are attenuated following Lrch4 knockdown, indicating that Lrch4 regulates upstream LPS signaling events. LPS-induced expression of the NF-kappaB-dependent cytokine TNFalpha was attenuated following Lrch4 knockdown at the level of both transcript and protein. Based on these and other findings, the inventors of this technology propose that Lrch4 may be a novel component of TLR receptor complexes and that modulation of Lrch4 activity might open up new opportunities for developing novel therapeutics for inflammatory diseases. CRADA Opportunity: The National Institute of Environmental Health Sciences (NIEHS) Laboratory of Respiratory Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Lrch4. Please contact Dr. Elizabeth M. Denholm at denholme@niehs.nih.gov for more information.

New Molecules for HIV Therapeutics: Fab, scFv, and Related Binding Molecules Specific for HIV-1 Rev

Wed, 30 Mar 2011 02:00:00 GMT
The invention offered for licensing and commercial development is in the field of HIV therapeutics. More specifically, the invention relates to methods and compositions for treating and/or inhibiting HIV infection or any other lentivirus. The invention describes the identification, though phage display, of a chimeric rabbit/human anti-Rev Fab (SJS-R1) that can inhibit polymerization of the HIV Rev protein and thus inhibit its normal function in virus replication. The Fab binds with very high affinity to a conformational epitope in the N-terminal half of HIV-1 Rev. The corresponding single chain antibody (scFv) was also prepared and characterized. Methods of making and using SJS-R1 Fab and SJS-R1 scFv, and antibodies and antibody fragments that share at least one CDR with SJS-R1 Fab, are provided. Specific described methods include methods of preventing or reversing polymerization of HIV Rev, methods of reducing infectivity of replication of a lentivirus, inhibiting Rev function in a cell infected with a lentivirus, and methods of treating a disease or symptom associated with Rev expression in an animal. CRADA Opportunity: The National Institute of Arthritis and Musculoskeletal and Skin Diseases, Protein Expression Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the technology. Please contact Cecilia Pazman, Ph.D. at 301-402-5579 for more information.

Agonistic Human Monoclonal Antibodies Against DR4

Tue, 15 Mar 2011 06:00:00 GMT
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been recognized as promising targets for cancer treatment. Therapeutics targeting TRAIL and its receptors are not only effective in killing many types of tumors but they also synergize with traditional therapies, and show efficacy against tumors that are otherwise resistant to conventional treatments.

The researchers at the NIH have developed two human monoclonal antibodies (mAbs) that bind to death receptor 4 (“DR4”). One of the mAbs is agonistic and inhibits the growth of ST486 cells with IC50 of about 10nM. The two mAbs were selected from a human phage-displayed Fab library by panning against a recombinant DR4 extracellular domain. Therefore the two mAbs are fully human. These antibodies could have considerable potential as cancer therapeutics alone or in combination with other drugs. Further, these antibodies could be used as a research tool for the study of DR4. CRADA Opportunity: The National Cancer Institute, Membrane Structure and Function Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize topic of invention or related laboratory interests. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell Carcinoma

Tue, 15 Mar 2011 10:00:00 GMT
Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is an extremely aggressive cancer syndrome with no effective treatment regimen and currently no cure. The progress of identifying HLRCC treatments and cures has likely been hindered due to the lack of an HLRCC model for studying the cancer syndrome and for screening therapeutic drug candidates.

This technology describes the UOK 268 cell line, a spontaneously immortalized renal tumor cell line that may be of great interest to industry for studying HLRCC, drug screening, and searching for tumor markers related to diagnosis, prognosis, and drug resistance. This cell line is only the second spontaneously immortalized cancer cell line of its kind in the world and is unique in that it is a primary tumor cell model (the other cell line, UOK 262, is from a metastasis cell model). The UOK 268 cell line is an established, clonal, immortalized renal cancer cell line derived from the long-term culture of aggressive tumor tissues of HLRCC in a specially designed culture medium under strict culture conditions. The UOK 268 exhibits an array of HLRCC kidney cancer characteristics that can promote protein and fatty acid biosynthesis and modulate HIF activities in a manner conducive to cancer cell proliferation.

Benefits:

This is only one of two immortalized HLRCC cell lines, and is unique in that it is from a primary tumor cell model.

Developing a diagnostic to search for tumor targets and screen for HLRCC and related cancers drug candidates will have significant benefits, including early detection and treatment.

CRADA Opportunity: The Center for Cancer Research, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize UOK268 as human HLRCC primary cell line model to comparing previously established UOK262, which was from metastasis lympho node. UOK 268 is a unique cell model for studying the underlying molecular derangements associated with impaired oxidative phosphorylation in cancer and for evaluating novel therapeutic approaches for this HLRCC-associated kidney cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Therapeutic Approach to Neurodegenerative Disorders Using a TFP5-Peptide

Tue, 15 Mar 2011 14:00:00 GMT
This invention discloses methods for treating neurodegenerative diseases by administering cyclin dependent kinase 5 (Cdk5) inhibitory peptides derived from P35, the activator of Cdk5. Abnormally hyperactive Cdk5 has been shown to be associated with a variety of neurodegenerative disorders. Disclosed in this invention are isolated peptide fragments, pharmaceutical compositions and methods for use of such for treating subjects with a neurodegenerative disease, such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD). An inhibitory fragment, TFP5, disclosed in this invention, has been shown to ameliorate symptoms of AD in disease animal models without any evidence of toxicity. In particular, TFP5 treatment of rat cortical neurons reduced hyperactivation of Cdk5 upon neuronal stress and insults. Following intraperitoneal (ip) injection, TFP5 was capable of crossing the BBB and localizing within the brain where it was found to rescue memory deficits and pathology in a double transgenic mouse (APP/PS1) AD model. CRADA Opportunity: The National Institute of Neurological Disorders and Stroke, Neuronal Cytoskeletal Protein Regulation Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize topic of invention or related laboratory interests. Please contact Heather Gunas, J.D., M.P.H., at 301-451-3944 or gunash@mail.nih.gov for more information.

Tiopronin Specifically Kills and Re-sensitizes Multi-Drug Resistant Cells to Chemotherapy

Tue, 15 Mar 2011 18:00:00 GMT
One of the major hindrances to successful cancer chemotherapy is the development of multi-drug resistance (MDR) in cancer cells. MDR is frequently caused by the increased expression or activity of ABC transporter proteins in response to the toxic agents used in chemotherapy. The increased expression or activity of the ABC transporter proteins causes the toxic agents to be removed from cells before they can kill the cell. As a result, research has generally been directed to overcoming MDR by inhibiting the activity of ABC transporters, thus causing the chemotherapeutic agents to remain in the cell long enough to exert their effects. However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects due to the inhibition of ABC transporter function in normal cells, thereby restricting their usefulness as therapeutics.

Investigators at the NIH have now discovered that the amino acid analog Tiopronin has the ability to kill multi-drug resistant cancer cells while leaving normal cells relatively unharmed. This suggests that Tiopronin can be developed as a therapeutic for multi-drug resistant cancers. Furthermore, Tiopronin re-sensitizes multi-drug resistant cells to chemotherapeutic agents over time. This may allow cyclical administration of chemotherapeutics without the development of permanent resistance to the agents, increasing the effectiveness of chemotherapy as a cancer treatment.

Importantly, Tiopronin is not an inhibitor of ABC transporter function because it kills multi-drug resistant cells without affecting the activity of ABC transporters. As a result, the undesirable side-effects that have prevented the use of inhibitors of ABC transporters as therapeutics should not affect the therapeutic application of Tiopronin. CRADA Opportunity: The National Cancer Institute, Multidrug Resistance Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Potential Chemotherapeutic Agents: Synthetic Peptide Inhibitors of the Wnt Pathway

Tue, 15 Mar 2011 22:00:00 GMT
Available for licensing are peptide inhibitors of the Wnt signaling pathway, a pathway that is activated in many cancer types. To date, there are few small molecules that target canonical Wnt/beta-catenin signaling and those that have been discovered have low potency and do not directly target beta-catenin, the pathway’s key signal mediator. The investigators have developed peptide inhibitors that selectively target a conserved region in beta-catenin essential for promoting cell growth but not cell adhesion and differentiation. Furthermore, these peptides have been synthetically modified to enhance cell penetration and structure stability thereby increasing their potency and efficacy. Interestingly, these peptides inhibit the canonical Wnt signaling pathway but not non-canonical Wnt signaling. As a result, these inhibitors potentially provide effective chemotherapies for tumors, such as colon and cervical, which depend upon canonical Wnt signaling. Moreover, as these inhibitors do not disrupt non-canonical Wnt signaling, which plays a role in kidney, lung, and vascular development, and they are likely to have minimal negative side effects. Additionally, these peptides can serve as an effective tool for researches to elucidate the roles of Wnt canonical and non-canonical signaling in development and many pathological conditions. CRADA Opportunity: The Center for Cancer Research, Cancer and Inflammation Program and Cancer and Developmental Biology Laboratory, are seeking statements of capability or interest from parties interested in collaborative research to further develop and commercialize Wnt pathway inhibitors. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Active Adaptive Detuning Systems to Improve Safety of Interventional Devices

Sat, 05 Mar 2011 03:00:00 GMT
The invention offered for licensing and commercial development is in the field of Interventional Magnetic Resonance Imaging (“iMRI”). More specifically the invention discloses interventional devices in which the heat generated at the device during the imaging process can be controlled to not exceed acceptable levels.

Active MRI compatible intravascular devices contain RF antenna to so that they are visible under MRI. However, these metallic structures may heat up significantly during interventional MRI procedures due to eddy current formation over the conductive transmission lines. The electrical field coupling between interventional devices and RF transmission coils strongly depend on the device position and orientation within the bore and insertion length of the device. Currently, conventional detuning circuit is used to decouple the conductive intravascular device during RF transmission phase of the MRI by activating the circuit with a PIN diode. However, conventional passive techniques do not adapt for each possible orientation or insertion length of the device. The current invention provides for a new active detuning system that adapts its circuit component to limit heating for every possible orientation and insertion length. The system reads out the received current signal value during RF transmission phase and changes the decoupling capacitor value by using varactor and integrated circuit components to reach new resonant condition (very high impedance). CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Peg Koelble at koelblep@nhlbi.nih.gov for more information.

Single Channel MRI Guidewire

Fri, 04 Mar 2011 08:00:00 GMT
The invention offered for licensing and commercial development is in the field of Interventional Magnetic Resonance Imaging (“iMRI”). More specifically the invention discloses a guidewire for magnetic resonance imaging with a single channel design to reduce complexity and to provide conspicuous tip visibility under MRI. In the design of the present device, the guidewire body includes an antenna formed from a rod and a helical coil coupled together. The helical coil can have multiple windings without a gap between the windings. The rod passes through the windings of the helical coil and is coupled to the helical coil using a conductive joint positioned at an end of the rod and at an end of the helical coil. Insulation can be positioned between the rod and the windings of the helical coil. The configuration allows visibility of the antenna along the length of a rod, except where it enters the windings of the coil. Thus, the tip visibility is enhanced as being separated from the rod. CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize technology involving single channel MRI guidewires. Please contact Peg Koelble at koelblep@nhlbi.nih.gov for more information.

System and Method for Monitoring and Controlling Radio Frequency Signals in Interventional Devices

Fri, 04 Mar 2011 13:00:00 GMT
The invention offered for licensing and commercial development is in the field of Interventional Magnetic Resonance Imaging (“iMRI”). More specifically the invention discloses interventional devices in which the heat generated at the device during the imaging process can be controlled to not exceed acceptable levels.

Interventional devices may heat up significantly during an interventional MRI procedure as a result of an RF induced current on the device. The RF induced current is caused by the coupling between the interventional device and RF electrical fields generated by the MRI. As the magnitude of the induced RF signal increases, the amount of heat that is generated also increases. The system of the present invention measures the induced RF signal and changes a decoupling capacitor value by using a varactor and a control circuit to adjust the impedance of the device and thus controls the magnitude of the RF signal. This unique design renders the device and the procedures done with it safe. CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize safety interventional devices during iMRI procedures. Please contact Peg Koelble at koelblep@nhlbi.nih.gov for more information.

Method for the Detection of a Subdural Hematoma Using a Handheld Hematoma Detector and Discriminator

Fri, 04 Mar 2011 18:00:00 GMT
The invention offered for licensing and further development is a device and method for detecting hematomas. The device is based on near infrared light emitted perpendicularly into a tissue from a non-stationary emitter and on continuous detection of the reflected light with a non-stationary probe. The device is designed as a handheld detector that can be used either in an ER or at the scene of an accident, which will allow the Doctor or EMT to diagnose hematoma for patients with a Traumatic Brain Injury at the scene. Furthermore, this device can be utilized to discriminate between subdural and epidural hematoma. The invention also discloses a novel method of data analysis is. The specific combination and sequences of data analysis are performed to discriminate healthy tissue from tissue perfused with blood. In addition, an interface to a laptop will be provided that creates a 3D surface image of the location of the hematoma is displayed. This invention will result in a better triage and treatment for patients with Traumatic Brain Injury (TBI) and fills a must filled gap in TBI health care. CRADA Opportunity: The National Institute of Child Health and Human Development, Section on Biomedical Stochastic Physics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the topic of this invention or related laboratory interests. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

System and Method for Automatic Speed Adaptation Control of a Treadmill

Fri, 04 Mar 2011 23:00:00 GMT
The invention offered for further commercial development relates to the coupling of virtual reality technology with a treadmill to implement goal-oriented walking practices effectively and to promote improved learning skills during gait training. The technology will be useful in rehabilitation of individuals with gait impairments resulting from Parkinson's disease, Traumatic Brain Injury, Stroke, Cerebral Palsy, and Spinal Cord Injury. In order to allow patients practice (e.g., voluntary change of walking speed in a natural way), software has been developed that automatically updates the velocity of a treadmill following the intention of the person walking on the treadmill. The invention uses a swing foot velocity measurement to control the velocity of the treadmill which can quickly and precisely detect the user's intention of changing walking velocity. Swing foot velocity measurement allows users to voluntarily change walking velocity while they have a realistic feel of walking (such as over-ground walking). We are seeking a CRADA collaborator to expand implementation of the invention into a fully integrated system that can control treadmill velocity in real time and can be reliably adapted to typical commercial treadmills. CRADA Opportunity: The National Institutes of Health Clinical Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize “A system and method for automatic speed adaptation control of a treadmill for patients.” Please contact Dr. Hyung S. Park at 301-451-7533 for more information.

Selective 12-Human Lipoxygenase Inhibitors for the Treatment of Diabetes and Clotting

Fri, 18 Feb 2011 04:00:00 GMT
This invention discloses small molecule inhibitors of human 12-lipoxygenase (12-hLO). 12-lipoxygenase expression, activation, and lipid metabolites have been implicated in type 1 and type 2 diabetes, cardiovascular disease, hypertension, Alzheimer’s, and Parkinson’s disease. The development of 12-hLO inhibitors may be a potent intracellular approach to decreasing the ability of platelets to form large clots in response to vessel injury or activation of the coagulation pathway. Thus, 12-hLO inhibition has the potential to attenuate platelet-mediated clot formation caused by diabetes and/or cardiovascular disease and significantly decrease the occurrence of myocardial infarction and death. Moreover, Type 1 and Type 2 diabetes are serious disorders that can lead to major complications and reduced lifespan. An unmet medical need is to identify new ways to protect beta cells in these metabolic disorders. A selective 12-hLO inhibitor could provide a new therapeutic approach to prevent or treat either form of diabetes. CRADA Opportunity: The NIH Chemical Genomics Center (NCGC), National Center for Advancing Translational Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these 12-hLO inhibitors. Please contact Dr. David Maloney at maloneyd@mail.nih.gov or Lili M. Portilla, MPA at 301-217-2589 or Lilip@nih.gov for more information.

Versatile Melanoma Antigen Family A3 (MAGE-A3) Specific Human T Cell Receptors to Treat Cancer that also Recognize Other MAGE-A Antigen Superfamily Members

Thu, 17 Feb 2011 09:00:00 GMT
Current approaches for treating cancer can also generate harsh side effects in patients and many cancer patients do not respond to generalized chemotherapy and radiation. New and improved therapeutic strategies need to be characterized by reduced side-effects and enhancements in specific anti-tumor activity in individual patients. Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual’s innate and adaptive immune system to fight against specific diseases, such as cancer. Scientists are aiming to improve cell transfer therapies by targeting an increasing collection of tumor antigens with more effective immune cell cultures.

T cell receptors (TCRs) are specialized proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of a variable domain that recognizes the antigen and a constant region that anchors the TCR to the membrane and transmits recognition signals by interacting with other proteins. When a TCR is activated by recognizing its antigen, such as a tumor antigen, signaling pathways are triggered in the cell to produce cytokines that mediate the immune response.

Scientists at the National Institutes of Health (NIH) have developed T cells genetically engineered to recognize melanoma antigen family A3 (MAGE-A3) peptide antigens. MAGE-A superfamily antigens, including MAGE-A3, are expressed primarily by tumor cells from a variety of cancers. Other than germ cells of the testis, normal cells do not express MAGE-A3 and other MAGE-A proteins, which makes these antigens ideal targets for developing cancer immunotherapies. There are twelve (12) known MAGE-A genes designated A1 – A12. The normal function of MAGE-A3 is not completely known, but in cancerous cells it appears to mediate fibronectin-controlled tumor growth and spreading. MAGE-A3 is one of the most widely expressed cancer testis antigens (CTAs) on human tumors and its expression increases as the cancer progresses to more advanced stages. The T cell receptors (TCRs) developed by these NIH scientists have specificity for MAGE-A3 and MAGE-A12 and deliver a robust immune response when they encounter tumor cells expressing these antigens. These TCRs also recognize MAGE-A2 and/or MAGE-A6, but to a lesser extent that MAGE-A3 and MAGE-A12. The ability to recognize antigens from multiple MAGE-A family members could allow these TCRs to be utilized in the treatment of multiple types of cancer in a wide array of cancer patients. Infusing cancer patients with MAGE-A3 specific T cells via adoptive immunotherapy could prove to be a powerful approach for selectively attacking tumors without generating toxicity against noncancerous cells. CRADA Opportunity: The National Cancer Institute Surgery Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of anti-MAGE-A T-cell receptors for the adoptive immunotherapy of cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Terahertz Spatial Light Modulator System for Adaptive Near-Field Imaging

Thu, 17 Feb 2011 14:00:00 GMT
The invention offered for licensing is in the field of imaging microscopes and relates to a terahertz light modulator system, and in particular to a terahertz spatial light modulator system for adaptive near-field imaging.

More specifically, the invention relates to a spatial light modulator system for adaptive near-field imaging having an optical source for transmitting an optical beam through a filter which is controlled to convert the optical light beam into a filtered optical light beam to define one or more transmission pathways through a photoconductive material. The system further includes a terahertz light source for transmitting a terahertz beam through one or more transmission pathways defined by the filtered optical light beam through the photoconductive material for illuminating and scanning the sample without the use of moving structural components. The device would allow micron-scale spatial resolution, would remove the need to mechanically scan a sample, and would allow automatic adjustment of image resolution and transmitted terahertz power. The near-field terahertz microscope of the invention could have a compact, fiber-coupled sensor head with no moving parts — ideal for scientific, medical, and industrial applications like crystal growth optimization, skin cancer diagnosis, and semiconductor chip inspection. In one application, such as "one-cut" surgery, the compact sensor head of the terahertz imaging system has the capability of distinguishing healthy cells from cancerous cells with micron-scale spatial resolution by immediately identifying a skin cancer margin without the need for laboratory work or additional surgery. In another application, the terahertz imaging system may be used in nondestructive semiconductor chip inspection since the terahertz imaging system provides micron-scale spatial resolution. CRADA Opportunity: The National Institute of Biomedical Imaging and Bioengineering is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Hari Shroff at hari.shroff@nih.gov or 301-435-1995 for more information.

Allele Specific shRNA for Nanog, and Its Use to Treat Cancer

Thu, 20 Jan 2011 19:00:00 GMT
Cancer stem cells are currently thought to be major participants in resistance to radiation therapy and chemotherapy; they are also thought to drive the spread of cancer through metastasis. It has been postulated that genes involved in early embryogenesis, primarily transcription factor Nanog but also Oct4 and SOX2, may be reactivated to maintain the properties of cancer stem cells, any treatment that inhibits such genes may therefore inhibit the progression of cancer and lead to improved survival and other clinical outcomes.

The NIH investigators discovered that the expression of NanogP8, a pseudogene of Nanog, is upregulated in human colorectal cancer spheroids formed in serum-free medium. NanogP8 has also been reported to be upregulated in human prostate cancer and glioblastomas. An inhibitory RNA molecule was identified by the investigators to knock down expression of NanogP8, without interfering with expression of Nanog. The discovery may improve the safety of a shRNA-based gene therapy and improve its chances for acceptance as a clinical therapy. CRADA Opportunity: The National Cancer Institute, Laboratory of Experimental Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this specific gene therapy to target colorectal and other human carcinomas. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

HMG3 for Detecting and Treating Diabetes

Fri, 21 Jan 2011 00:00:00 GMT
This invention relates to the use of High Mobility Group N 3 (HMGN3) as a marker for detecting diabetes and as a therapeutic agent for treating diabetes.

Diabetes is disabling largely because commonly available anti-diabetic drugs do not adequately control blood sugar levels to completely prevent the occurrence of high and low blood sugar levels. Inappropriate blood sugar levels can be toxic and can cause long-term complications including renopathy, retinopathy, neuropathy and peripheral vascular disease. Those with diabetes are also at risk for developing related conditions such as obesity, hypertension, heart disease and hyperlipidemia.

This invention relates to the discovery that reduced expression of HMGN3 (also called TRIP7) gives rise to elevated blood glucose levels, reduced serum insulin levels and impaired glucose tolerance. CRADA Opportunity: The National Cancer Institute, Laboratory of Metabolism, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HMGN and related chromatin-binding proteins in the function of pancreatic islet cells. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Fluoroquinolone Derivatives as Inhibitors of Human Tyrosyl-DNA Phosphodiesterase (Tdp1)

Thu, 20 Jan 2011 05:00:00 GMT
Chemotherapy can provide therapeutic benefits in many cancer patients, but it often ultimately fails to cure the disease since cancer cells can become resistant to the chemotherapeutic agent. To overcome these limitations, additional strategies are needed to restore or amplify the effect of antitumor agents. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme involved in the repair of DNA lesions created when the activity of the Topoisomerase 1 (Top1) is inhibited. Tdp1 has been regarded as a potential therapeutic co-target of Top1 in that it seemingly counteracts the effects of Top1 inhibitors, such as camptothecin. By reducing the repair of Top1-DNA lesions, Tdp1 inhibitors have the potential to augment the anticancer activity of Top1 inhibitors.

The NIH investigators discovered fluoroquinolone derivatives as specific Tdp1 inhibitors that could potentiate the pharmacological action of Top1 inhibitors, which are currently used in cancer treatment. The instant invention discloses a method of treating cancers with a therapeutically effective amount of a Top1 inhibitor, and a fluoroquinolone derivative that inhibits Tdp1 activity. CRADA Opportunity: The Center for Cancer Research, Laboratory of Molecular Pharmacology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize tyrosyl-DNA-phosphodiesterase inhibitors. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

A Computer Program to Predict Optimal Sites on Protein Sequences for Production of Peptide-Directed Antibodies (NHLBI AbDesigner)

Thu, 20 Jan 2011 10:00:00 GMT
The invention offered for licensing is a computer program called "NHLBI AbDesigner" that allows the user to input a unique identifier for an individual mammalian protein to be analyzed in order to find out what short peptides in its amino sequence would most likely result in a strong immunogenic response when injected into a research animal. The software displays standard predictors of immunogenicity and antigenicity in easy-to-view heat maps and also allows users to choose peptides most likely to elicit antibodies that are specific to said protein. The computer code is written in Java and would be made available in the form of .jar files.

For additional information please refer to: https://dirweb.nhlbi.nih.gov/labs/LKEM_G/LKEM/Pages/Antibodydesignsoftware.aspx. CRADA Opportunity: The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Brian Bailey, Ph.D. at 301-594-4094 or bbailey@mail.nih.gov for more information.

Diagnosis and Treatment of Cancer Through NUAK2 Assessment and Modulation

Fri, 07 Jan 2011 15:00:00 GMT
The present invention describes that high levels of expression of both NUAK2 and phosphor-Akt at Ser473 (p-Akt) predict the survival of patients with acral melanomas and that modulation of NUAK2 expression using gene therapy approaches effectively suppresses tumor growth of melanoma cells. Furthermore, a CDK inhibitor targeting CDK2, which is a downstream target of NUAK2, effectively suppresses the tumor growth of melanoma cells with NUAK2 amplification. CRADA Opportunity: The National Cancer Institute, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the regulation of NUAK2 function as a strategy to treat melanoma and predict the survival of patients with acral melanomas. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

GATA-3 Reporter Plasmids for Revealing Underlying Mechanisms in Breast Cancer

Tue, 21 Dec 2010 20:00:00 GMT
Scientists at the National Institutes of Health (NIH) have developed GATA-3 gene reporter plasmids that express a green fluorescent protein (GFP) or luciferase reporter protein under the control of a GATA-3 promoter. Cells expressing this plasmid will glow fluorescent green or emit light energy, respectively, if GATA-3 gene expression is activated in the cells. The reporter construct allows cells where GATA-3 gene expression is activated to be isolated and collected for further analysis or be monitored in the host environment.

GATA-3 is a transcription factor that is highly expressed in several types of cells and is a critical transcription factor for the development of particular lineages of hematopoietic cells and normal mammary luminal epithelium. GATA-3 plays a regulatory role in determining the fate of cells in the hematopoietic systems and the mammary gland. Disruption of GATA-3 expression leads to defects in the development of sub-types of lymphoid cells and luminal mammary epithelial cells. GATA3 expression is highly associated with luminal sub-types of breast cancer, whereas expression of GATA3 is low or undetectable in basal subtypes of breast cancer which often have a poor prognosis. Low or limited GATA-3 expression is correlated with larger tumors, increased likelihood of tumor-positive lymph nodes, and predicts an overall poorer clinical outcome compared to patients with higher mammary GATA-3 expression. Researchers believe that a better understanding of GATA-3 function and its dysregulation during the onset and progression of breast cancer will lead to new strategies in diagnosing and treating the disease. CRADA Opportunity: The Center for Cancer Research, Laboratory of Cancer Biology and Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize GATA-3 Reporter Plasmids for Revealing Underlying Mechanisms in Breast Cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Modulators of Survival Motor Neuron Production

Fri, 10 Dec 2010 01:00:00 GMT
This technology discloses compounds that modulate the amount of Survival Motor Neuron protein (SMN). Low levels of SMN protein are associated with Spinal Muscular Atrophy (SMA), which constitutes a group of inherited diseases that cause progressive muscle degeneration leading to death. Consequently, therapeutic inventions have focused on increasing SMN protein levels. This invention discloses novel arylthiazolyl piperidines which are shown to be modulators of SMN production. This invention also discloses methods of treating SMA by administering SMN protein modulators. CRADA Opportunity: The NIH Chemical Genomics Center (NCGC), National Center for Advancing Translational Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these SMN modulator compounds. Please contact Dr. Juan Marugan at maruganj@mail.nih.gov for more information.

Use of Sterculic Acid to Treat Choroidal Neovascularization

Wed, 08 Dec 2010 06:00:00 GMT
Sterculic acid is a naturally occurring cyclopropene acid present in kapok seed oil, cottonseed oil, and in the seeds of the Sterculia foetida tree. Sterculic acid has been reported to be a non-specific inhibitor of stearoyl-Co desaturase (SCD), which has been implicated in several disease states, including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, skin disease, hypertension, neurological diseases, immune disorders and cancer (Ntambi JM, J. Lipid Res., 1999, 40(9):1549-1558). NIH investigators have recently discovered that sterculic acid inhibits the neovascularization of the chick chorioallantonic membrane demonstrating that this compound exhibits a potent anti-angiogenic activity. Further, the NIH investigators have shown that sterculic acid inhibits the formation of choroidal neovascularization in the retina of laser treated rats. These results suggest that sterculic acid possesses anti-angiogenic effect likely through regulating genes involved in the angiogenic process.

The present invention is directed to methods of using sterculic acid for the treatment of inflammation, in particular, 7-ketocholesterol mediated inflammation, 7-ketocholesterol cytotoxicity, or unregulated angiogenesis. Diseases mediated by 7-ketocholesterol-induced inflammation and 7-ketocholesterol cytotoxicity include atherosclerosis age-related macular degeneration, and Alzheimer's disease. Diseases mediated by unregulated angiogenesis include certain cancers and age-related macular degeneration. Also disclosed are methods of treating atherosclerosis or Alzheimer's disease using sterculic acid. CRADA Opportunity: The National Eye Institute (NEI), Laboratory of Retinal Cell and Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize sterculic acid, and its derivatives for the treatment of diseases related to angiogenesis or mediated by 7-ketocholesterol-induced inflammation. Please contact David L. Whitmer, Technology Development Coordinator, NEI, at 301-496-4876 or whitmerd@mail.nih.gov for more information. Click here to view the NEI collaborative opportunity announcement.

Nitisinone for Treatment of Oculocutaneous/Ocular Albinism and for Increasing Pigmentation

Wed, 08 Dec 2010 11:00:00 GMT
Albinism (also called achromia, achromasia, or achromatosis) is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect in any one of a number of proteins involved in the production of melanin. Certain forms of albinism are known to be due to mutations in tyrosine metabolism. In oculocutaneous albinism (OCA), pigment is lacking in the eyes, skin and hair. In ocular albinism, only the eyes lack pigment. Patients with albinism experience varying degrees of vision loss associated with foveal hypoplasia, nystagmus, photophobia and/or glare sensitivity, refractive errors, and abnormal decussation of ganglion cell axons at the optic chiasm. Current treatment options for vision problems caused by albinism are limited to correction of refractive errors and amblyopia, low vision aids, and (in some cases) extraocular muscle surgery.

Nitisinone (NTBC) is an FDA-approved drug used in the treatment of tyrosinemia, type 1. The drug blocks the normal degradation pathway of tyrosine thus allowing greater circulating plasma levels of tyrosine. NIH investigators have identified that administration of NTBC to subjects (e.g., mice or humans) with certain forms of albinism, can result in increased circulating tyrosine levels, an increase in tyrosinase activity, and, subsequently, increased pigmentation.

This technology provides methods for increasing tyrosine plasma concentrations in patients suffering from oculocutaneous albinism or ocular albinism by administering a pharmaceutically acceptable composition of NTBC. Specifically, this technology can be useful in treating patients with type OCA1a albinism, who possess no measurable tyrosinase activity, or type OCA1b albinism, who exhibit greatly diminished tyrosinase activity.

Applications for this technology include treatment of impaired vision in patients suffering from oculocutaneous albinism, or ocular albinism, and as a treatment for increasing pigmentation in the eyes, hair and/or skin of patients. CRADA Opportunity: The National Eye Institute, Ophthalmic Genetics and Visual Function Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of nitisinone (NTBC) for oculocutaneous albinism or as a treatment for increasing pigmentation in the eyes, hair and/or skin of patients. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information. Click here to view the NEI collaborative opportunity announcement.

Pyruvate Kinase M2 Activators for the Treatment of Cancer

Wed, 08 Dec 2010 16:00:00 GMT
NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.

The invention described here is a series of small molecules that activate pyruvate kinase (PK) isoform M2. PK-M2 is a critical metabolic enzyme that is affected in all forms of cancer. Inactivation of PK-M2 leads to a buildup of metabolic intermediates inside the cell. Tumor cells require a buildup of metabolic intermediates in order to undergo rapid cell growth and proliferation. Hence, activation of PK-M2 in tumor cells may prevent the buildup of metabolic intermediates and thereby stall tumor cell proliferation or destroy the tumor cells. Further, while in normal post-embryonic cells only PK isoforms R, L, or M1 are active, in all tumors only PK-M2 is active. So, PK-M2 activation would affect only tumor cells, and small-molecule PK-M2 activators may not be toxic to healthy cells.

This invention discloses the use of two new small molecule pharmacophores that can activate PKM2 through the allosteric site: 3-oxo-3,4-dihydro-2H-benzo [b] [1,4] oxazine-7-sulfonamides, and 2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamides. CRADA Opportunity: The NIH Chemical Genomics Center (NCGC), National Human Genome Research Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these pyruvate kinase M2 activators. Please contact Dr. Matthew Boxer at boxerm@mail.nih.gov for more information.

Synovial Sarcoma X Breakpoint-2 (SSX-2) Specific Human T Cell Receptors for Treating a Wide-Range of Cancers

Fri, 26 Nov 2010 21:00:00 GMT
Many current approaches for treating cancer also generate harsh side effects in patients. In addition, a sizable patient population does not respond to generalized chemotherapy and radiation treatments for cancer. There is an urgent need to develop new therapeutic strategies aimed at reducing side-effects and increasing specific anti-tumor activity in individual patients. Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual’s innate and adaptive immune system to fight against specific diseases, including cancer. As research and development continues in this area, scientists continue to improve cell transfer therapies by targeting an increasing collection of tumor antigens with more effective immune cell cultures.

T cell receptors (TCRs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit recognition signals by interacting with other proteins. When a TCR is stimulated by an antigen, such as a tumor antigen, some signaling pathways activated in the cell lead to the production of cytokines, which mediate the immune response.

Scientists at the National Institutes of Health (NIH) have developed T cells genetically engineered to recognize synovial sarcoma X breakpoint-2 (SSX-2) peptide antigens. SSX proteins, including SSX-2, are expressed primarily by tumor cells from a variety of cancers, including pancreatic cancer where very few treatment options exist. Other than germ cells of the testis, normal cells do not express SSX proteins and, thus, should not be targeted by therapies directed against these proteins. Therefore, SSX proteins represent a promising target for cancer immunotherapy. There are ten (10) known members of the SSX protein family designated SSX-1 through SSX-10. The T cell receptors (TCRs) developed by these NIH scientists have specificity for SSX-2 and deliver a robust immune response when they encounter SSX-2 expressing cells. However, these TCRs also recognize five (5) other SSX family members, including SSX-3, SSX-4, SSX-5, SSX-9, and/or SSX-10, and deliver a productive, intermediate immune response in the context of target cells expressing these antigens. This versatile antigen coverage could allow these SSX-specific TCRs to be utilized in the treatment of multiple types of cancer in a wide array of cancer patients. Infusing cancer patients with SSX-2 specific T cells via adoptive immunotherapy could prove to be a powerful approach for selectively attacking tumors without generating toxicity against noncancerous cells. CRADA Opportunity: The National Cancer Institute, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of T cell receptor gene therapy for the treatment of cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Novel Compositions and Methods to Treat Glioblastoma and Other Cancers

Sat, 27 Nov 2010 02:00:00 GMT
There remains a significant unmet need for therapeutics to treating glioblastoma multiforme, a very aggressive type of brain tumor. Glioblastoma is difficult to treat with conventional surgery, chemical, and radiation therapies. With approximately 18,000 new glioblastoma cases in the U.S. each year, and a comparable market in Europe, the global market for such products forecast to be over $300 million. In light of the high unmet need in malignant astrocytoma and little in the way of pipeline competition, this indication represents a potential easy route to market for new drugs.

Researchers at the National Cancer Institute (NCI) have identified two novel molecular targets, annexin 1 (Anx A1) and its receptor formyl peptide receptor 1 (FPR1), for new anti-glioblastoma therapies. Anx A1 and FPR1 mediate growth, invasion, production of angiogenic factors, tumor formation, and are abnormally expressed by more highly malignant glioblastomas. Depletion of Anx A1 in glioblastoma cells resulted in their reduced capacity to form tumors; additional depletion of FPR1 further reduced this capacity. Further, the NCI researchers have found a correlation between Anx A1 expression and the degree of malignancy of human gliomas.

Novel anti-glioblastoma therapies encompassed by this invention include neutralizing antibodies against Anx A1 and FPR1, small compound agonists of Anx A1 and FPR1, small interference RNAs (siRNAs) that deplete Anx A1 and FPR1 from glioblastoma cells, as well as delivery methods to effectively administer the Anx A1 and FPR1 targeting drugs into brain tissues. CRADA Opportunity: The Center for Cancer Research, Laboratory of Molecular Immunoregulation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Targeted Anti-Cancer Compounds for Treating Chromosomal Instability Syndromes

Fri, 26 Nov 2010 07:00:00 GMT
At $47 billion, cancer is one of the largest, fastest growing markets in the pharmaceutical industry. There remains a significant unmet need for new therapeutics that target cancer cells while sparing normal cells. Cancer cells show higher levels of DNA damage than normal cells, and therefore rely more heavily than normal cells on DNA repair mechanisms for survival. There is a particular need for cancer therapies for cancer-prone chromosomal instability syndromes such as Ataxia Telangiectasia, Nijmegen Breakage, Bloom, and Fanconi’s anemia, which result from dysfunctional DNA repair systems.

Researchers at Columbia University and the National Cancer Institute (NCI) have developed compositions and methods of useful in the treatment of cancer and in the sensitization of cancer cells to cancer therapy. The compositions target the MRE11-RAD50-NBS1 (MRN) complex, a DNA repair complex essential for sensing and responding to DNA damage.

Given the dependency of cancer cells on DNA repair systems, they are susceptible to compositions that inhibit DNA damage repair. Thus, cancers that already have one or more defects in DNA repair systems, such as those from patients with chromosomal instability syndromes, are effectively treated with the present compositions. CRADA Opportunity: The National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize agents for the prevention and treatment of cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

ERBB4 Mutations Identified in Human Melanoma Metastasis Cell Lines (2690, 2379, 2197, 2183, 2535, 2645, 1770, 2359, 2238, 2319, 2190)

Fri, 26 Nov 2010 12:00:00 GMT
Protein tyrosine kinases (PTKs) have been associated with a wide variety of cancers, including melanoma. Using high-throughput gene sequencing, the NIH has analyzed PTKs in melanoma and identified several novel somatic alterations, including alterations in ERBB4 (also called HER4). These mutations were found to increase the sensitivity of cells in which they reside to small molecule inhibitors, such as lapatinib.

Available for licensing are several melanoma cell lines that harbor ERBB4 mutations. These cell lines provide methods of identifying specific inhibitors to ERBB4 that could be used to treat patients with ERBB4 mutations as well as methods to further understand the role of ERBB4 mutations in melanoma. Given the recent success of small molecule protein kinase inhibitors and specifically inhibitors to epidermal growth factor receptor (EGFR) (such as gefinitib and erlotinib), these reagents could be used to further the development of specific inhibitors to ERBB4 and improve existing melanoma treatments for patients with these mutations. CRADA Opportunity: The National Human Genome Research Institute’s Cancer Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate and/or commercialize these newly characterized ERBB4 mutant cell lines as well as to identify and test ERBB4 inhibitors as possible therapeutic drug candidates to treat melanoma and other cancers. Please contact Dr. Yardena Samuels at samuelsy@mail.nih.gov for more information.

Isocitrate Dehydrogenase 1 (IDH1) R132 Mutation Human Melanoma Metastasis Cell Line

Fri, 26 Nov 2010 17:00:00 GMT
Isocitrate dehydrogenase 1 (IDH1) plays an important role in glucose metabolism in the cytoplasm, converting isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+ to NADPH). However, when IDH1 harbors a R132 mutation it results in the accumulation of 2-hydroxyglutarate and has a corresponding association with cancer. This mutation in IDH1 has previously been identified in approximately 80% of progressive gliomas and 10% acute myeloid leukemias (AML). In contrast, this mutation is very rare in other cancers. Therefore, additional research on the IDH1 R132 mutation could be useful for diagnostic, prognostic, and therapeutic purposes.

The researchers at the NIH have developed a human melanoma cell line designated 2633, which harbors the IDH1 R132C mutation. The inventors used low passage cell lines derived from a panel of confirmed metastatic melanoma tumor resections, paired with apheresis-collected peripheral blood mononuclear cells to identify IDH1 mutations. Sequencing of IDH1 in this panel allowed them to discover a melanoma cell line with the IDH1 R132C mutation. Until now no such cell line has been found and this has hindered the understanding of the effects mutated IDH1 has on cancer progression as well as the development of drugs that would be specific for cells that harbor this mutation. Use of this cell line will allow researchers decipher the biology of this gene as well as aid in the development of specific inhibitors of its mutated form. CRADA Opportunity: The National Human Genome Research Institute’s Cancer Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate and/or commercialize this newly identified melanoma-associated gene as a diagnostic marker as well as utilize the IDH1 R132 cell line to identify and test IDH1 inhibitors as possible therapeutic drug candidates to treat melanoma and other cancers. Please contact Dr. Yardena Samuels at samuelsy@mail.nih.gov for more information.

Novel Compounds that Specifically Kill Multi-Drug Resistant Cancer Cells

Fri, 26 Nov 2010 22:00:00 GMT
One of the major hindrances to successful cancer chemotherapy is the development of multi-drug resistance (MDR) in cancer cells. MDR is frequently caused by the increased expression or activity of ABC transporter proteins in response to the toxic agents used in chemotherapy. The increased expression or activity of the ABC transporter proteins causes the toxic agents to be removed from cells before they can act to kill the cell. As a result, research has generally been directed to overcoming MDR by inhibiting the activity of ABC transporters, thus causing the chemotherapeutic agents to remain in the cell long enough to exert their effects. However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects due to the inhibition of ABC transporter function in normal cells, thereby restricting their usefulness as therapeutics.

Investigators at the NIH previously identified novel compounds with the ability to kill multi-drug resistant cancer cells while leaving normal cells relatively unharmed. These “MDR-selective compounds” were not inhibitors of ABC transporters because they killed multi0drug resistant cells without affecting the activity of ABC transporters. Furthermore, their activity was dependent directly on the level of expression of ABC transporters, thus increasing their selectivity for diseased cells. As a result, the undesirable side-effects that have prevented the use of inhibitors of ABC transporters as therapeutics should not affect the therapeutic application of the MDR-selective compounds.

The inventors have now generated third generation MDR-selective compounds with further improved solubility, selectivity and killing activity toward MDR cells. The new MDR-selective compounds selectively kill MDR cancer cells, and their efficacy correlates directly with the level of ABC transporter expression. This suggests that the third generation MDR-selective compounds represent a powerful strategy for treating MDR cancers. CRADA Opportunity: The Center for Cancer Research, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.Click here to view the NCI collaborative opportunity announcement.

Scanningless Multi-photon Microscopy with Diffraction-Limited Axial Resolution

Wed, 10 Nov 2010 03:00:00 GMT
The technology offered for licensing is a scanningless multiphoton microscope for performing 3-dimensional imaging that achieves diffraction-limited resolution. The microscope combines temporal multiplexing with spatial dispersion to achieve diffraction-limited resolution without having to mechanically scan the sample (a field of view up to 30x30 microns). The wide-field excitation of the sample allows imaging rates in excess to prior art multiphoton microscopes while still achieving diffraction-limited axial resolution. The microscope includes a laser source that generates a femtosecond laser beam that passes through a stair-step optic having a variable thickness piece of glass arranged such that each "strip" of the laser beam is delivered at a different relative delay. Each strip exits the stair-step optic and is imaged onto the surface of a diffraction grating by two imaging lenses and a mirror. The diffraction grating sends the different wavelengths that compose each horizontal strip of the laser beam in different directions. Another pair of lenses, such as the imaging lens and objective lens (e.g., high numerical aperture objective) images and de-magnifies the surface of the diffractive grating into a biological sample that causes an excitation to occur in the sample. The ensuing excitation generates fluorescence in the sample confined to the focal plane of the objective lens, where the excitation is maximized. The fluorescence is collected through the objective lens and then by a CCD camera. CRADA Opportunity: The National Institute of Biomedical Imaging and Bioengineering Section on High Resolution Optical Imaging is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this invention. Please contact Dr. Henry Eden at edenh@mail.nih.gov for more information.

Novel Anti-HIV Acylthiol Drugs and Thioether Prodrugs

Tue, 09 Nov 2010 08:00:00 GMT
The inventions provide the compositions, pharmaceutical carrier, and usages of the new Acylthiols (E-329-2000 family) and Thioether pro-drug (E-177-2010 family) compounds in treatment of retroviral infections such as HIV. More specifically, these compounds target the highly-conserved nucleocapsid protein of HIV-1. Activity of these compounds against the nucleocapsid protein leads to inactivation of the virus via disruption of the zinc fingers, integral for infectivity, without significantly affecting cellular proteins. Finally, these inventions can be prepared from inexpensive starting materials and two “one-pot” reactions. Thus, they open the possibility for an effective drug treatment for HIV that could reach underdeveloped countries. These new compounds have the potential to be used both as a systemic drug for the treatment of HIV-1 infection and as a topically-applied barrier to prevent viral transmission. CRADA Opportunity: The Laboratory of Cell Biology, Center for Cancer Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the above invention for the treatment/prevention of HIV infection. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

System for Magnetic Resonance Spectroscopy of Brain Tissue for Pattern-based Diagnostics

Fri, 29 Oct 2010 12:00:00 GMT
Available for licensing and commercial development is a system for preprocessing magnetic resonance spectroscopy (MRS) data of brain tissue for pattern-based diagnostics. The MRS preprocessing system includes an MRS preprocessing module that executes an operation that normalizes MRS spectrum data, recalibrates and scales the normalized MRS spectrum data, and then renormalizes the scaled MRS spectrum data. The resulting preprocessed MRS data is used to assist in identifying abnormalities in tissues shown in MRS scans. Raw MRS spectrum data and scaling the raw MRS spectrum data is achieved by a plurality of weighting constants to generate a preprocessed MRS spectrum data. The method may also include providing raw MRS spectrum data, recalibrating the raw MRS spectrum data, and scaling the recalibrated MRS spectrum data by using a plurality of weighting constants to generate a preprocessed MRS spectrum data. CRADA Opportunity: The FDA National Center for Toxicological Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize FDA’s magnetic resonance spectroscopy technology in various imaging and diagnostic applications. Please contact Alice Y. Welch, Ph.D. at 301-796-8449 or alice.welch@fda.hhs.gov for more information.

Stimulation of Natural Killer T-cell Anti-tumor Activity

Wed, 27 Oct 2010 16:00:00 GMT
Natural killer T cells (NKT) are a unique lymphocyte population that has T-cell and NK cell functional properties in order to rapidly elicit an immune response. alpha-galactosylceramide (alpha-GalCer) is a potent NKT stimulator and induces of IFN-gamma release to promote immunity against tumors and infectious agents. Humans have natural antibodies against alpha-galactose, which may be one of the reasons why the human clinical trials of alpha-GalCer or KRN7000 were not very successful.

Investigators at the National Cancer Institute have found that beta-mannosylceramide (beta-ManCer) promotes immunity in an IFN-gamma independent mechanism. beta-ManCer is a new class of NKT agonist that induces immune responses alone, through nitric oxide and TNF-alpha-dependent mechanisms, or synergistically with alpha-GalCer to enhance alpha-GalCer’s efficacy. Since beta-ManCer does not have alpha-galactose, which can be neutralized by natural antibodies, patients could be treated with multiple doses without negative side effects associated with the loss of IFN-gamma production. Hence, beta-ManCer is a promising anti-cancer treatment either alone or in combinatorial therapies with alpha-GalCer to selectively induce immune responses. CRADA Opportunity: The Vaccine Branch of the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize beta-ManCer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Diagnostic and Prognostic HCC-related Metabolites

Wed, 27 Oct 2010 20:00:00 GMT
Metabolite profiling identifies and measures changes in cellular metabolites as a means to determine a direct correlation between gene expression and changes in biological function. Investigators at the National Cancer Institute have identified a unique set of metabolite biomarkers associated with hepatocellular carcinoma (HCC), early stage HCC, HCC patient outcome and HCC stem-cell subtype. Subsets of this metabolite/gene signature can distinguish HCC tumors from normal tissues with 88-97% accuracy, identify early stage HCC patients with 62-78% accuracy, wherein early stage is defined as TNM stage I, prognose negative patient outcome, and identify a HCC stem cell subtype with 70-77% accuracy. These metabolites and gene surrogates are elements of the PI3K and Myc signaling networks which can potentially be targeted for therapeutic purposes.

HCC represents an extremely poor prognostic cancer, and patients are often diagnosed with end-stage cancer and have poor survival. HCC is also a very heterogeneous disease and often arises from chronic liver disease. Surgery and transplantation remain the only curative option for patients; however, complications due to cirrhosis mean it is a viable option for 5-10% patients. This HCC gene signature can be developed into assays to enable clinicians to accurately diagnose HCC, including early stages and subtype of this disease, and therefore stratify patients for appropriate treatment and prioritizing liver transplantation candidates based on their metabolite profile. CRADA Opportunity: The Center for Cancer Research, Laboratory of Human Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize metabolomic signatures for liver cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Modified POTE Peptides for Cancer Immunotherapy

Fri, 22 Oct 2010 00:00:00 GMT
Investigators at the National Cancer Institute have identified and enhanced immunogenicity of POTE epitopes to improve their efficacy in cancer vaccines. POTE is a novel tumor antigen expressed in a variety of cancers including breast, prostate, colon, lung, ovary, and pancreas cancers. POTE has limited expression in normal tissues and therefore a specific target for cancer treatments, including immunotherapy. Immunotherapy has great potential as a cancer therapeutic because of its specificity and freedom from toxic effects of chemotherapies.

Antigen-specific cancer immunotherapy often relies on identification of epitopes expressed by cancer cells that can be targeted by cytotoxic T cells (CTL). However, the CTL repertoire against high-affinity cancer epitopes is often ineffective because cancer epitopes may share a similar structure to natural “self” antigens. As a result, cancer cells are not recognized by CTLs and destroyed. The enhanced POTE epitopes induce a stronger immune response than natural responses. These modified epitopes are more effective at inducing CTL against POTE expressing cancer cells and have greater potential to serve as cancer vaccine targets. CRADA Opportunity: The Center for Cancer Research, Vaccine Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

IL-10 and IFN-gamma Peptide Inhibitors

Thu, 21 Oct 2010 04:00:00 GMT
Available for licensing are several potent and selective inhibitors of IL-10 and IFN-gamma signaling. Although cytokines play important roles in cancer and inflammation, there are no specific inhibitors of any cytokines to date. IL-10 and IFN-gamma cytokine signaling play crucial roles in inflammation, cancer growth, and autoimmune diseases. The investigators have developed short peptides that potently and selectively interfere with dimerization of the cytokines and their binding to the corresponding receptor. Included in the patent application are also metabolically stable lipopeptides mimicking conserved regions of IL-10 and IFN-gamma receptors that interfere with STAT3 and STAT1 phosphorylation and subsequent signaling. Lipopeptides potently inhibit STAT3 and STAT1-dependent growth of cancer cells. These compounds are promising drug candidates for the treatment of cancer and many infectious and inflammatory diseases. CRADA Opportunity: The Center for Cancer Research, Cancer and Inflammation Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize inhibitors of IL-10, IFN-gamma and STAT3 signaling. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Immunotoxin for the Treatment of Neuroblastoma Relapse

Thu, 21 Oct 2010 08:00:00 GMT
Immunotoxins are proteins which have two distinct domains: (1) an antibody or antibody binding fragment which is capable of recognizing a single specific cell surface protein and (2) a toxin domain which is capable of inducing cell death. Immunotoxins are currently being pursued as therapeutics because they specifically kill diseased cells while leaving essential, healthy cells alone. This increases the effectiveness of the therapy while reducing the appearance of side-effects. A particular immunotoxin that is being studied in clinical trials consists of an anti-CD22 antibody binding fragment and a mutated Pseudomonas exotoxin A. Although this immunotoxin is being explored primarily as a treatment for hematological malignancies, it can be used to treat any condition where CD22 is overexpressed on the cell membrane of diseased cells.

Neuroblastomas are malignant cancers that start in nerve tissue and primarily affect infants and children. Although frontline treatments for neuroblastoma are often effective, relapse frequently occurs in high risk cases. The most common form of relapse in neuroblastoma patients is caused by Neuroblastoma tumor initiating cells (NB-TIC). Therefore, if NB-TIC could be eliminated, high risk neuroblastoma patients could have a therapeutic option for preventing a relapse.

This invention concerns the discovery that NB-TIC expresses CD22. As a result, NB-TIC are susceptible to treatment with an anti-CD22 immunotoxin. By combining frontline neuroblastoma treatments with anti-CD22 immunotoxins, both the primary neuroblastoma and cells capable of initiating a relapse can be eliminated. As a result, even high risk neuroblastoma patients should have an increased chance of surviving neuroblastoma. CRADA Opportunity: The Center for Cancer Research, Pediatric Oncology Branch and Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize recombinant anti-CD22 immunotoxins for the treatment of neuroblastoma. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Novel Prognostic and Therapeutic Biomarker for Cancer and Inflammatory Diseases

Thu, 21 Oct 2010 12:00:00 GMT
There remains a significant unmet need for diagnostics, prognostics, and therapeutics for conditions that involve inflammation and the formation of blood clots such as bleeding disorders, trauma, and diseases such as sepsis, cardiovascular disease, stroke, and cancer. The global market for such products is varied and competitive, and is forecast to be over $40 billion by 2010.

Researchers at the National Cancer Institute (NCI) have identified that levels of a novel soluble protein involved in the repair mechanism for damaged blood vessels correlate with outcome in sepsis and with the diagnosis of disseminated intravascular coagulation, a contributing factor to the morbidity and mortality associated with sepsis.

Further, the NCI researchers have demonstrated that a recombinant version of this novel protein facilitates the clotting of blood, suggesting a potentially significant therapeutic benefit for the treatment of bleeding disorders or trauma. CRADA Opportunity: The Center for Cancer Research, Cancer and Inflammation Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize soluble TREM receptor proteins. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Soluble Glypican-3 Protein for Treatment of Cancer

Thu, 21 Oct 2010 16:00:00 GMT
Hepatocellular carcinoma (HCC) is a form of liver cancer that is among the more deadly cancers in the world. HCC is typically only detected at the later stages of cancer development, which is always associated with poor prognosis. Because HCC is often associated with liver disease, traditional chemotherapy is not an option, making surgery the most common form of treatment. As a result, there is a need for new treatments.

Glypican-3 (GPC3) is a cell surface protein that is normally involved in cell growth and differentiation. GPC3 has been shown to act through the Wnt-signaling pathway, a pathway that is often activated in a number of different cancer cell types. Significantly, the ability of GPC3 to activate signaling through Wnt requires that GPC3 be bound to the cell membrane. GPC3 is also preferentially expressed on HCC cells, suggesting it could play a particularly important role in tumorigenesis in HCC.

This invention concerns a soluble form of GPC3 that lacks its cell membrane anchoring domain. This soluble form of GPC3 maintains its ability to interact with the Wnt signaling pathway, but cannot induce the activation of the pathway because it is not bound to the cell membrane. By competing with fully functional GPC3, the soluble GPC3 is able to inhibit the growth of HCC cells, thereby decreasing the ability of tumors to grow and metastasize. This suggests that soluble GPC3 represents a possible therapeutic for HCC. CRADA Opportunity: The National Cancer Institute, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Prevention and Treatment of Herpes Virus Infection by Inhibition of the JMJD2 Family of Histone Demethylases

Tue, 12 Oct 2010 20:00:00 GMT
Investigators at the NIH have discovered a potential means for preventing or treating a herpes virus infection by inhibiting the activity of the host cell’s histone demethylases. When herpesviruses enter a cell, they are inactivated by cellular defense mechanisms that wrap the viral genome in repressive chromatin structures. In order for viral replication to progress, the host’s own histone demethylases are recruited to the viral genome to reverse this repression. In a preceding invention, the laboratory disclosed that viral replication and reactivation can be significantly reduced through inhibition of the histone demethylase LSD1 using Mono-Amino Oxidase Inhibitors (MAOIs); drugs that are in clinical use. The current invention further discloses that inhibition of a second set of histone demethylases (JMJD2 family) using a specific JMJD2 inhibitor, dimethyloxaloylglycine (DMOG), also results in significant repression of herpes viral replication.

Either alone or in combination, small molecule inhibition of LSD1 and the JMJD2 family present novel approaches for preventing herpes virus infection and halting viral reactivation that can lead to a disease that ranges from mild core sores to herpesvirus keratitis and life threatening encephalitis. Additionally, chromatin-mediated repression of viral genomes and the requirement to de-repress these genomes for productive infection appears to be general to herpesviruses. Therefore, this treatment could also be applicable to chicken pox, shingles, CMV disease, mononucleosis, and Kaposi's sarcoma. CRADA Opportunity: The NIAID Laboratory of Viral Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize prevention and treatment of viral diseases. Please contact Thomas Kristie, Ph.D. at 301.496.3854 or tkristie@niaid.nih.gov for more information.

Inverse Agonists of the TSH Receptor for the Treatment of Thyroid Cancer and Hyperthyroidism

Wed, 13 Oct 2010 00:00:00 GMT
This technology features small molecule inverse agonists of the thyroid-stimulating hormone (TSH) receptor that may be readily synthesized, and are likely to prove effective for oral administration. These compounds may potentially be used to treat recurrent thyroid cancer and some cases of hyperthyroidism, and also represent unique tools for investigating the role of TSH receptor signaling in these diseases.

According to the National Cancer Institute, over 37,000 new cases of thyroid cancer were diagnosed in the United States in 2008. Approximately 10% to 30% of patients thought to be disease-free after initial treatment will develop recurrent cancer or metastases, and unless the recurrence is detected early, the prognosis is generally poor.

As the TSH receptor is known to stimulate proliferation of thyroid cancer cells, it has been suggested that suppression of basal TSH receptor signaling may improve outcomes in the treatment of recurrent thyroid cancer. The compounds disclosed in this technology suppress basal signaling by the TSH receptor, and are thus excellent candidates for a suppression-based treatment approach. CRADA Opportunity: The NIDDK Office of Technology Transfer and Development is seeking statements of capability or interest from parties interested in collaborative research to further develop inverse agonists of the TAS receptor. Please contact Marguerite J. Miller at 301-496-9003 or millermarg@mail.nih.gov for more information.

Compositions and Methods for the Treatment of Cancer

Mon, 27 Sep 2010 04:00:00 GMT
Cancer is the second leading cause of human death next to coronary disease in the United States. Worldwide, millions of people die from cancer every year. In the United States alone, as reported by the American Cancer Society, cancer causes the death of well over a half-million people annually, with over 1.2 million new cases diagnosed per year. While deaths from heart disease have been declining significantly, those resulting from cancer generally are on the rise. Cancer is soon predicted to become the leading cause of death in the United States.

This application claims methods for inducing an immune response to a tumor. These methods include administering a therapeutically effective amount of apoptotic tumor cells conjugated to a K-type CpG oligodeoxynucleotide (ODN) to a subject. Methods for treating a tumor in a subject are also claimed in this application. These methods include administering a therapeutically effective amount of apoptotic tumor cells conjugated to a K-type CpG oligodeoxynucleotide (ODN) to a subject. More specifically, the tumor cells may be autologous, and the tumor may be a lymphoma, cervical cancer, prostate cancer, breast cancer, colon cancer, or a lung cancer. CRADA Opportunity: The Center for Cancer Research, Laboratory of Experimental Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Linked Purine Pterin HPPK Inhibitors Useful as Antibacterial Agents

Mon, 27 Sep 2010 08:00:00 GMT
The invention offered for licensing describes and claims novel inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthetic pathway which is essential for microorganisms but absent in mammals. These novel inhibitors are based on linked purine pterin compounds. They can disrupt the folate biosynthesis of bacteria and thus can find utility as potential antimicrobials. Antibiotics based on these lead molecules can be specifically designed and synthesized to serve as broad-spectrum or narrow-spectrum antibiotics. None of the currently established antibiotics target HPPK. CRADA Opportunity: The National Cancer Institute, Biomolecular Structure Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the inhibitors of HPPK as novel antibiotics. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

A Rapid, Peripheral Blood Gene Expression Biomarker Panel for Diagnosis of Acute Ischemic Stroke

Mon, 20 Sep 2010 12:00:00 GMT
There are presently no rapid, accurate diagnostic procedures or methods that can be used to determine whether a patient has suffered an acute ischemic stroke (AIS). Current technologies for diagnosis of AIS are limited by speed and resources as well as inaccuracy and generally require a high level of training to interpret the results for medical technicians. In contrast, this invention may lead to the development of a rapid and accurate clinical diagnostic kit that would require very little training for proper use and could be used in the field or the emergency room setting.

Scientists at the National Institutes of Health have discovered that expression levels of a set of nine genes may be used as biomarkers for diagnosis of AIS as well as outcome prediction. These biomarkers may be rapidly identified using peripheral whole blood and may form the basis of a rapid and accurate clinical point of care diagnostic kit.

Further, if validation is positive, this technology may enable rapid differential diagnosis between acute ischemic stroke and hemorrhagic stroke, transient ischemic attack, or any pathology mimicking a stroke. Not only can this be used to identify stroke earlier in the course of treatment, this panel may also help to better characterize stroke subtype, and identify new pathways for stroke treatment. This is important as the only FDA approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) and tPA must not be given to hemorrhagic stroke patients since it could increase intracranial bleeding. To effectively treat AIS, tPA must be administered intravenously within 3-4 hours of known stroke onset. Because the differential diagnosis of AIS versus hemorrhagic stroke is difficult without specialized imaging equipment such as a CT scan with contrast or an MRI image, only a small percentage of stroke patients (3-5%) are ever given tPA. So, a rapid and accurate clinical diagnostic kit based on this invention would have a profound public health benefit and likely a large commercial potential. CRADA Opportunity: The NINR is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a point of care test for ischemic stroke diagnostics and outcome prediction. Please contact Dr. Taura Barr at 304-293-0503 or barrt@mail.nih.gov for more information.

Small Molecule Neuropeptide S Receptor (NPSR) Antagonists for the Treatment of Addictive Disorders, Mood, Anxiety and Sleep Disorders

Mon, 20 Sep 2010 16:00:00 GMT
The inventors, who work for the National Human Genome Research Institute (NHGRI) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) at the National Institutes of Health (NIH), have developed NPSR antagonists that hold the potential for being clinically useful treatments for alcohol and drug addiction. Neuropsychiatric disorders including, for example, mood, anxiety, eating, and sleep related disorders, as well as alcoholism and drug addiction, are major causes of mortality and morbidity. Patient relapse into drug seeking and use, after an interval of sobriety, is a key component of the addictive syndrome, with approximately two-thirds of patients relapsing within three months of initiating abstinence. Therefore, relapse prevention is a major treatment objective.

Neuropeptide S (NPS), an endogenous ligand for the Neuropeptide S receptor (NPSR) has recently been shown to play a key role in relapse-like behavior. In addition, because mood, anxiety, eating, and sleep related behaviors are often closely linked with the addictive process, and are also affected by the NPS system, it is believed that the NPSR antagonist will also be promising as a useful therapeutic target in these clinical areas as well. CRADA Opportunity: The NIH Chemical Genomics Center (NCGC), NHGRI, NIH is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these NPSR antagonist small molecule compounds for various therapeutic uses including treatment of neuropsychiatric disorders and alcohol and drug addiction. Please contact Dr. Juan J. Marugan at maruganj@mail.nih.gov for more information.

Use of Adenosine Agonists to Prevent Arterial Vascular Calcification Disorder

Mon, 20 Sep 2010 20:00:00 GMT
Scientists at the National Human Genome Research Institute (NHGRI) and the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) have discovered a genetic defect in the Ecto-5’-nucleotidase (NT5E) gene which results in Cluster of Differentiation 73 (CD73) deficiency that leads to a decrease in adenosine, and ultimately, an increase in vascular calcification. NT5E encodes CD73, an enzyme that converts adenosine monophosphate (AMP) to adenosine in the extracellular region of the vascular endothelium. Normally, extracellular adenosine binds to one of the several receptors on the surface decreasing the production of cyclic AMP (cAMP) resulting in an inhibition of vascular calcification.

The discovery of this genetic mutation leading to a decrease in adenosine provides a method of treating or preventing the disorder by using adenosine receptor agonists as therapeutic agents. Adenosine receptor agonists can be used to treat or prevent disorders associated with vascular and/or joint capsule calcification, including for example atherosclerosis, Monkeberg’s medial sclerosis, CD74 deficiency, Ehlers Danlos syndrome (EDS), Marfan/Loewe Dietz syndrome, fibromuscular dysplasia, Kawasaki syndrome, pseudoxanthoma elasticum, and premature placental calcification. CRADA Opportunity: The NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize adenosine receptor agonist compounds for therapeutic use including as a treatment of certain common as well as rare vascular calcification-related disorders (see above Description of Invention). Please contact NHGRI Technology Development Coordinator Claire T. Driscoll at cdriscol@mail.nih.gov for more information.

Transplant and Autoimmune Therapy Using T-Cells Expressing Programmed Death Ligand-1 (PD-L1)

Tue, 21 Sep 2010 00:00:00 GMT
Transplant complications (graft rejection and graft-versus-host disease) and autoimmune diseases are primarily caused by T cell immune responses against normal host tissue or transplanted tissues. These disorders can lead to serious complications and may be chronic, debilitating, and fatal. Current treatment for these disorders is oftentimes not effective, and is typically associated with significant side effects, including global immune suppression, which increases the rate of infection and cancer. Hence, there is a need for new technologies to more specifically suppress the immune system for treatment of these diseases.

Programmed death (PD) ligand 1 (PD-L1) is an immune molecule present on regulatory T cells (Tregs), other suppressor cell populations, and tumor cells; the function of PD-L1 is to suppress the function of pathogenic T cells that express the PD1 receptor. Therefore, it has been hypothesized that the transfer of T cells that are enriched for PD-L1 expression might represent an effective method to suppress autoimmunity or transplant complications. Adoptive T cell therapy using Tregs is one such approach; however, this approach is limited due to the relative rarity of Tregs and their tendency to possess differentiation plasticity towards pathogenic T cell subsets such as the Th17 subset. Ex vivo co-stimulated and expanded effector T cells can be generated in sufficient numbers for cell therapy; however, such cells are not enriched for PD-L1 expression.

The current technology overcomes these limitations through transduction of co-stimulated T cells with a lentiviral expression vector that dictates T cell expression of PD-L1. In this method, the co-stimulated T cells acquire the immunosuppressant characteristics of Treg cells. The PD-L1 gene expression construct co-expresses a cell surface molecule (i.e., CD19 or CD34) that allows enrichment of the gene-modified T cells to high purity. Also the construct co-expresses another gene, TMPK, which acts as a safety cell fate switch because the TMPK can specifically activate the cytotoxic prodrug, AZT. By incorporation of this TMPK/AZT cell fate safety switch, the current technology will allow for PD-L1 therapeutic delivery, with subsequent elimination of the therapeutic cells in the event of toxicity. CRADA Opportunity: The Center for Cancer Research, Experimental Transplantation and Immunology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Methods for Treatment and Diagnosis of Psychiatric Disorders

Mon, 20 Sep 2010 04:00:00 GMT
Current drugs used to treat schizophrenia block dopamine receptors. These drugs can effectively suppress the “positive” symptoms of schizophrenia but have little impact on the debilitating or “negative” symptoms of the disease which include social withdrawal, emotional unresponsiveness, difficulty with attention and memory, and apathy. There is thus a therapeutic need for improved antipsychotics that can improve both positive and negative symptoms. This technology describes novel interactions between neuregulins (NRGs), ErbB receptors, and dopamine signaling pathways that may influence the expression of schizophrenia. Researchers at the NIH demonstrated that NRGs reverse long term potentiation (LTP) when given shortly after LTP is established without affecting basal transmission. Blockade of ErbB receptors with antagonists prevented depotentiation by NRG, and NRG showed no effect in an ErbB-4 knockout mouse model. Thus NRG regulation of LTP occurs through the ErbB-4 receptor. Data also showed that dopamine antagonists block the effects of NRGs on LTP. These findings could be useful in the development of antipsychotic drugs that block NRG actions, and in doing so, provide better therapies for schizophrenia.

This technology describes methods of treating schizophrenia with an antagonist that blocks neuregulin-1 activation of the ErbB-4 receptor signaling pathway, methods of identifying schizophrenia in affected patients, as well as methods of identifying modulators of ErbB-4 receptor signaling. This technology may also be applicable for treating or preventing other psychiatric disorders such as, bipolar disorder, attention deficit disorder (ADD), and autism. CRADA Opportunity: The National Institute of Child Health and Human Development, Section on Molecular Neurobiology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Fenoterol and Fenoterol Analogues for Treatment of Glioma, Glioblastoma, and Astrocytoma

Thu, 09 Sep 2010 08:00:00 GMT
To date there is no effective treatment for the brain tumors or brain cancers indentified as gliomas, glioblastomas, or astrocytomas.

This technology relates to the discovery that fenoterol and related analogues block astrocytoma and glioblastoma cell division at low doses. In a xenograft model utilizing the 1321N1 astrocytoma tumor implanted in the flank of SKID mice, the (R,R)-4-methoxyfenoterol analogue significantly decreased tumor growth relative to a control group receiving vehicle and studies utilizing [³H]-(R,R)-4-methoxyfenoterol have shown that the compound readily passes the blood-brain barrier. The anti-tumor effect is associated with the ability of fenoterol and related analogues to induce production of cyclic adenosine monophosphate (cAMP), which is normally decreased in glioblastomas and astrocytomas. Induced cAMP production inhibits brain tumor growth in vivo. Fenoterol and related analogues are beta-2 adrenergic receptor (beta2 AR) agonists and the anti-tumor effect is associated with the expression of this receptor. Since there is a heterogeneous expression of beta2 AR in human brain tumors, patients who will respond to fenoterol therapy can be predetermined leading to individualized treatment. In addition to use in the initial treatment of brain tumors, the systemic and CNS bioavailability of the drug after oral administration and the minimal systemic toxicity suggest that fenoterol and it analogs can be used in the adjuvant treatment of patients with beta2 AR-positive gliomas, glioblastomas or astrocytomas. Studies with a number of fenoterol analogs and CNS-implanted tumors are in progress.

The fenoterol analogues discussed in this technology are subject to HHS Ref. No. E-205-2006/3 (U.S. Patent Application No. 12/376,945 and PCT Publication No. WO/2008/022038). CRADA Opportunity: The National Institute on Aging, Laboratory of Clinical Investigation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of fenoterol and fenoterol analogs in the front line and adjuvant treatment of CNS tumors and other beta2 AR expressing tumors. Please contact Nicole Guyton, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information. Click here to view the NIA collaborative opportunity announcement.

Assay for Arf GTP-binding Proteins

Thu, 09 Sep 2010 12:00:00 GMT
The worldwide laboratory research reagents market is expected to surpass $13 billion in 2010, and the field of biotechnology appears key to maintaining the market's growth. Antibodies are becoming increasingly significant, especially for targeting the diseased cells and cell compounds.

Researchers at the National Cancer Institute (NCI), NIH, have developed an antibody-based assay that measures levels of Arf GTP-binding proteins, some of which have been linked to the invasive behavior of cancer cells. The assay is robust, can be performed both on cell lysates and fixed cells, and can distinguish among specific endogenous Arf-GTP isoforms. CRADA Opportunity: The Center for Cancer Research, Laboratory of Cellular and Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Superresolution Microscopy via Azicon Beam Polarization Devices

Tue, 31 Aug 2010 16:00:00 GMT
The technology offered for licensing pertains to novel polarizers that produce tangentially and radially polarized beams. The polarizers and polarizing beam splitter of the technology include one or more pairs of axicons (also known as conical lenses) that are configured to separate an input beam into a radially polarized component and a tangentially (or azimuthally) polarized component. A second axicon pair can be positioned to recombine the tangentially polarized component so as to provide a more uniform beam intensity. The radial polarized component can be reflected or otherwise directed so that one or both the radial and tangential components are available for use. CRADA Opportunity: The NHLBI Laboratory of Molecular Biophysics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Brian Bailey at 301-594-4094 for more information.

Tempol: A Commercially Available Nitroxide as Cancer Therapeutics

Mon, 23 Aug 2010 20:00:00 GMT
The invention is the discovery that a commercially available stable nitroxide, namely TEMPOL can effectively reduce the level of hypoxia-inducible transcription factor (HIF)-2alpha. Elevated HIF-2alpha is associated with clear cell kidney cancer characterized by mutation of the VHL tumor suppressor gene and with many other cancers. Therefore, TEMPOL can potentially be developed into a cancer drug to treat patients with elevated HIF-2alpha, whether due to compromised VHL function or not. CRADA Opportunity: The Center for Cancer Research, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of Tempol to target HIF-2alpha in cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Chimeric Anti-human ROR1 Monoclonal Antibodies

Tue, 24 Aug 2010 00:00:00 GMT
Available for licensing are mouse anti-human receptor tyrosine kinase-like orphan receptor 1 (ROR1) monoclonal antibodies (mAbs). ROR1 is a signature cell surface antigen for B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) cells, two incurable B-cell malignancies that are newly diagnosed in approximately 15,000 and 3,500 patients per year, respectively, in the United States. Currently, there are no therapeutic mAbs that specifically target B-CLL or MCL cells. Anti-ROR1 mAbs may be linked to chemical drugs or biological toxins thus providing cytotoxic delivery to malignant B-cells and not normal cells. Additionally, these antibodies can be fused to radioisotopes and can be used to diagnose B-CLL and MCL malignancies. CRADA Opportunity: The Center for Cancer Research, Experimental Transplantation and Immunology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-ROR1 mAbs, antibody-drug conjugates, radioimmunoconjugates, bispecific antibodies, and other therapeutic or diagnostic modalities. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

System and Method for Producing Nondiffracting Light Sheets that Improves the Performance of Selective Plane Illumination Microscopy (SPIM)

Mon, 23 Aug 2010 04:00:00 GMT
The technology offered for licensing relates to a system and method of producing nondiffracting beams of light that spatially overlap, but do not interfere with each other when intersecting the detection plane of an optical arrangement. The system includes an illumination source (i.e. ultrafast laser) for transmitting a beam of light through the optical arrangement that includes a diffraction grating for diffracting the light beam to produce beams of light having different wavelengths, which are then passed through an annular aperture that transforms the beams of light into nondiffracting beams having different wavelengths. The method can be readily utilized in Selective Plane Illumination Microscopy (SPIM), a system that provides optical sectioning of a sample that is labeled with fluorescent dyes. SPIM can provide quantitative three-dimensional maps of the distribution of a flurophore within the sample with high spatiotemporal resolution and an excellent signal-to-noise ratio. The standard SPIM technique however produces nonuniform axial resolution, which is caused by the diffraction of the laser beam through the sample, causing degradation in the optical sectioning, and forcing a compromise between field of view and axial resolution. Techniques for decoupling field of view and axial resolution have previously utilized nondiffracting beams (e.g. Bessel beams) for sample illumination. The resulting interference from multiple nondiffracting beams degrades the quality of optical sectioning and the quality of the image. The present technology utilizing nondiffracting noninterfering beams is intended to alleviate the problems associated with the currently used SPIM techniques. CRADA Opportunity: The NIBIB Section on High Resolution Optical Imaging is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the nondiffracting Light Sheets for SPIM. Please contact Hari Shroff at 301-435-1995 or hari.shroff@nih.gov for more information.

Method of Producing Immortalized Primary Human Keratinocytes for HPV Investigation, Testing of Therapeutics, and Skin Graft Generation

Mon, 23 Aug 2010 08:00:00 GMT
One of the major limitations of using cultured keratinocytes for research studies is that primary keratinocytes senesce after a few passages. Keratinocytes from specific anatomical sites are also difficult to culture. Scientists at the NIH have demonstrated that primary keratinocytes, from several anatomical sites, when treated with a small-molecule inhibitor of the ROCK protein maintain a proliferative state and become immortal without genetic modification to the cells. Keratinocytes are also the host cells for human papillomaviruses (HPVs) and other viruses and this technology enables the study of those viruses that do not immortalize cells. In addition, this technology may enhance the quantity of material available for skin grafts, as current grafting techniques are limited by the amount of donor material immediately available. Thus, this technology may provide an ideal model environment for producing large quantities of both normal and diseased primary human keratinocytes from small numbers of primary cells from individual hosts or anatomical sites for research purposes, testing of therapeutics, skin graft generation and HPV investigation. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Viral Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of producing immortalized primary human keratinocytes. Please contact Johanna Schneider, Ph.D. at 301-451-9824 or schneiderjs@niaid.nih.gov for more information.

Novel Drugs for the Treatment of Schizophrenia

Mon, 23 Aug 2010 12:00:00 GMT
Because psychosis and cognitive decline are among the most common debilitating afflictions of humans, the search for new treatments is very important and timely.

Researchers at the NIH have found that genetic variations on the PIK3CD gene are associated with schizophrenia in Caucasian and African American families and can affect normal human cognition functions such as memory, IQ and executive cognition. The inventors have shown that an inhibitor of the phosphatidylinositol 3-kinase p110 delta (PIK3CD) enzyme, which is encoded by the PIK3CD gene, significantly improves a migratory response that is critically impaired in schizophrenic patients. This drug, as well as other PIK3CD inhibitors, could provide effective treatments of psychosis and cognitive decline. CRADA Opportunity: The National Institute of Mental Health Clinical Brain Disorders Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the development of PIK3CD inhibitors for the treatment of CNS disorders including schizophrenia, psychosis, and cognitive deficiency. Please contact Amanda Law at lawa@mail.nih.gov for more information.

Melanocyte Pigmentation or Proliferation with Neuregulin: Compositions and Methods to Treat Skin Disorders, Including Skin Cancer

Tue, 17 Aug 2010 16:00:00 GMT
Human skin pigmentation is regulated by complex and intricate interactions among melanocytes and keratinocytes in the epidermis and fibroblasts in the dermis. A number of factors secreted from keratinocytes and/or from fibroblasts have been shown to be involved in regulating skin pigmentation after UV exposure. NIH investigators have previously demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. Now, using microarray analysis to compare gene expression patterns in 15 different primary dermal fibroblast populations derived from the dorsal trunk skin of three different skin phototypes (I, III and VI), these investigators have identified a number of genes that differ dramatically in expression. One among them, neuregulin 1 (NRG-1), secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting it is one of the major factors determining human skin color. NRG-l was observed to be highly expressed by fibroblasts derived from darker skin. NIH investigators believe that NRG-1 increases the proliferation of human melanocytes via the phosphorylation of Akt. These results suggest a potential role for NRG-1 in regulating constitutive human skin color and perhaps its dysfunction in pigmentary skin diseases. Based on these observations, NIH investigators are currently developing compositions and methods of modulating pigmentation and proliferation of a melanocyte to prevent or treat skin disorders, including skin cancer. CRADA Opportunity: The Center for Cancer Research, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of NRG-1 (or modifiers of its function) to regulate skin pigmentation. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Matrix Metalloproteinase-9 Blade-1 Region Peptides: Use as Cell Migration Modulators

Tue, 17 Aug 2010 20:00:00 GMT
Matrix metalloproteinase-9 (MMP-9) is an enzyme integrally involved in many normal physiological processes that require degradation and remodeling of the extracellular matrix, such as cell migration and invasion, wound repair, bone remodeling, angiogenesis, and embryonic growth. MMP-9 is shown to be involved in the progression of several diseases including many cancers, cardiovascular diseases, CNS diseases, respiratory diseases, and arthritis. In cancer, MMP-9 is thought to promote growth, migration, and spread of cancer cells by catalyzing the degradation of extracellular matrix proteins, releasing bound growth factors, and allowing cancer cells to escape from the primary tumor.

NIH inventors have discovered that specific polypeptides corresponding to Blade-1 region of MMP-9 hemopexin domain can stimulate migration of cells, specifically the migration of cells expressing beta1 integrin. The present technology can be used to develop novel therapeutic candidates for the prevention and treatment of human disease conditions mediated by MMP-9 promoted cell migration, e.g., cancer, inflammation, fibrotic diseases, cardiovascular diseases, CNS diseases, respiratory diseases, angiogenesis and arthritis. CRADA Opportunity: The National Institute of Environmental Health Sciences, Laboratory of Molecular Carcinogenesis, Cell Adhesion Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Elizabeth M. Denholm, Ph.D. at 919-541-0981 or denholme@mail.nih.gov for more information.

Glioblastoma Diagnostics and Therapeutics

Thu, 12 Aug 2010 00:00:00 GMT
Investigators at the NIH have discovered an Anti-TNF Induced Apoptosis (ATIA) protein, which protects cells against apoptosis. ATIA is highly expressed in glioblastoma and astrocytomas and its inhibition results in increased cell sensitivity to TNF-related apoptosis-inducing ligand induced cell death. Hence, ATIA assays may enable clinicians to effectively stratify patients for appropriate treatment. ATIA exists in a soluble form that can be detected in culture medium of ATIA expressing cells indicating it could be used to develop a non-invasive, blood based diagnostic test such as an ELISA. Glioblastomas and astrocytomas can be diagnosed via MRI and CT scans; however, these scans cannot detect tumor type, i.e. glioblastoma vs. medulloblastoma. The investigators found that ATIA is induced in cells under hypoxia conditions. More importantly, knockdown of ATIA in human glioblastoma cells renders cells to apoptosis under hypoxia conditions. Therefore, ATIA is a potential novel therapeutic target for treating human glioblastoma.

Glioblastoma arise from astrocytes, cells that provide neurons structural and metabolic support. Glioblastomas account for twenty percent of primary brain tumors and fifty percent of astrocytomas. These indications are designated as rare diseases as there is an annual 2-3 newly diagnosed cases of glioblastoma per 100,000 people in the United States whereas the astrocytoma incidence rate is 1.22 cases per 100,000 for individuals aged 0-19 years in the United States. CRADA Opportunity: The National Cancer Institute, Cell and Cancer Biology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

N-Methanocarba Adenosine Derivatives and Their Dendrimer Conjugates as A₃ Receptor Agonists

Wed, 11 Aug 2010 04:00:00 GMT
This technology relates to specific (N)-methanocarba adenine nucleosides that have been developed and dendrimers that connect these compounds to create molecules with multiple targets. Dendrimers are essentially repeated molecular branches presenting the core receptor-binding molecules. The compounds synthesized function as agonists and antagonists of a receptor of the G-protein coupled receptor (GPCR) superfamily. In particular, the receptors of interest for this invention include A₃ adenosine receptors and agonists and antagonists of P2Y receptors, such as P2Y₁ and P2Y₁₄.

Dendrimer conjugates may have one or more advantages, such as increased solubility, reduced toxicity, and improved pharmacokinetic properties. They can also be used to connect other types of molecules without affecting the agonist or antagonists properties. For instance, molecules such as those used for imaging or tracing can be added. Dendrimers can also be used to link more than one type of agonist or antagonist to confer multiple functionalities. This technology provides a novel mechanism to treat a number of disorders related to dysregulation of A₃ adenosine receptors. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, Molecular Recognition Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Dr. Kenneth Jacobson at kajacobs@helix.nih.gov for more information.

A Novel Scaffold for Multivalent Display of Ligands

Wed, 11 Aug 2010 08:00:00 GMT
Multivalent interactions are important in cell attachment, wound healing and immune responses. Such interactions are associated with cancer metastasis, blood clotting and the generation of antibodies from a vaccination. Mimicking multivalent interactions on a synthetic scaffold is challenging especially when large numbers of ligands (such as 5 or more) need to be displayed. There are numerous synthetic scaffolds that have been developed, but there are significant limitations that remain.

Scientists at the NIH have designed a novel multivalent scaffold that can display anywhere from 1 to 200 ligands. This system allows different types of ligands to be displayed in a controlled, spatially-addressable manner. This system uses peptide nucleic acids (PNAs) containing gamma-substituted side chains. PNAs are synthetic molecules that possess the bases derived from DNA. This invention could revolutionize the way in which multivalent display is used in research as well as help make vaccinations or prevent disease. CRADA Opportunity: The NIDDK Laboratory of Bioorganic Chemistry is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this novel scaffold or to collaborate on related laboratory interests. Please contact Marguerite J. Miller at 301-496-9003 and/or millermarg@niddk.nih.gov for more information.

Immortalized Human Bronchial Epithelial Cell Line

Fri, 23 Jul 2010 12:00:00 GMT
Normal cells can be cultured in vitro for a limited period of time before they exhibit a "crisis" or senescence, wherein they display abnormal cell morphology and significant reduction or cessation of cell proliferation. Investigators at the National Cancer Institute developed immortalized cell line by isolating bronchial epithelial cells from non-cancerous individuals and subsequent infection with an adenovirus 12-SV40 virus hybrid. Unlike normal cells, the immortalized cells be cultured continuously in vitro in suitable medium and retain features of normal human bronchial epithelial cells, including the absence of invasive behavior in vitro or in vivo. These cells can also be transfected with oncogenes and used as a model for multistage carcinogenesis, or employed to assay a biological or chemical agent's ability to induce differentiation and carcinogenesis as well as test potential chemotherapeutic agents. CRADA Opportunity: The Center for Cancer Research, Laboratory of Human Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Immortalized Human Bronchial Epithelial Cell Line. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Use of Cucurbitacins and Withanolides for the Treatment of Cancer

Fri, 23 Jul 2010 16:00:00 GMT
Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2).

The protein TRAIL has a very interesting characteristic that it can preferentially cause death of cancer cells whereas normal non-transformed cells are unaffected. Thus use of TRAIL or agonist antibodies to its so-called "death receptors" has been a current focus in cancer therapy. CRADA Opportunity: The Center for Cancer Research, Laboratory of Experimental Immunology, Cancer Inflammation Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of certain cucurbatacins or withanolides in combination with pro-apoptotic agonists of TRAIL death receptors for cancer therapy. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Software for Accurate Segmentation of Cell Nuclei in Breast Tissue

Fri, 23 Jul 2010 20:00:00 GMT
Automatic segmentation of cell nuclei is critical in several high-throughput cytometry and pathology applications (1), such as spatial analysis of genetic loci by fluorescence in situ hybridization ("FISH"), whereas manual segmentation is laborious (2). Current automated segmentation methods have varying performance in the presence of distortions introduced during sample preparation, non-uniform illumination, clustering of the individual objects of interest (cells or cell nuclei), and seldom assess boundary accuracy.

Researchers at the National Cancer Institute-Frederick, NIH, have developed an automatic algorithm to segment cell nuclei (3) and FISH signals from two-dimensional images of breast tissue. This automated system integrates a series of advanced image processing methods to overcome the delays inherent to current manual methods for segmenting (delineating) individual cell nuclei in tissue samples. The system automatically selects a subset of nuclei that with high likelihood are accurately segmented. This system has been validated using both simulated and actual datasets that have been accurately analyzed by manual methods. The system generalizes to independent analysis of many spatial parameters useful for studying spatial gene positioning in interphase nuclei, and potentially has a wide range of diagnostic pathology, cytological and high throughput screening applications. CRADA Opportunity: The inventers, working for the Office of the Director, National Cancer Institute, are seeking statements of capability or interest from parties interested in collaborative research (using the Cooperative Research and Development Agreement (CRADA) or Material Transfer Agreement (MTA)) to further develop, evaluate, or commercialize the software for accurate segmentation of cell nuclei and FISH signals in tissue sections. Collaborators working in the field of quantitative and automated pathology may be interested. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Software System with Applications in Clinical Prognosis, Personalized Medicine and Clinical Research

Sat, 24 Jul 2010 00:00:00 GMT
Available for licensing is software that can provide prognostic information for different diseases and in particular for cancer. The software can determine whether a particular genotype has a significant association with survival time for an individual receiving treatment. For example, it can determine if a specific genetic pattern is associated with an increased or decreased time to recurrence of a particular type of cancer for patients on a given treatment regimen. CRADA Opportunity: The NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Treatments for Smith-Lemli-Opitz Syndrome and Other Disorders of Cholesterol Biosynthesis

Mon, 12 Jul 2010 04:00:00 GMT
This technology provides methods for treating Smith-Lemli-Opitz Syndrome and other disorders of cholesterol biosynthesis.

Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder caused by an inborn error of cholesterol biosynthesis. It affects an estimated one in 20,000 to 60,000 newborns, and is most prevalent in Caucasians of Central European ancestry. It is characterized by distinctive facial features, microcephaly, mental retardation or learning disabilities, and behavioral problems, as well as malformations in many parts of the body, such as the heart, lungs, kidneys, gastrointestinal tract, and genitalia. However, the clinical manifestations of this disease can vary widely, ranging from relatively moderate symptoms to profoundly severe and life-threatening symptoms. At least 95% of SLOS patients present with some degree of mental retardation and learning disability.

Biochemically, SLOS is caused by disruption of the DHCR7 gene, which is responsible for the final step in the production of cholesterol; this results in low cholesterol levels and an accumulation of toxic byproducts of cholesterol biosynthesis in the blood, nervous system, and other tissues. Supplementary dietary cholesterol is provided to SLOS patients, but is often of limited clinical benefit; because levels of byproducts remain high, they may interfere with the uptake of free cholesterol.

Although some of the behavioral and learning problems are due to developmental problems, a portion of these symptoms are likely due to a biochemical disturbance. That biochemical disturbance is potentially treatable.

In their recent work, the inventors have discovered that the accumulation in SLOS cells of the cholesterol precursor 7-DHC causes abnormal sphingolipid storage and transport, resulting in a cellular phenotype similar to that observed in the lysosomal storage disease Niemann-Pick type C (NPC). They have also discovered that treatment with inhibitors of sphingolipid biosynthesis corrects these abnormalities, and thus such inhibitors are of potential therapeutic benefit for the treatment of SLOS, as well as for other diseases exhibiting similar defects in sphingolipid trafficking.

This technology claims compounds that inhibit sphingolipid biosynthesis for use in treating diseases which have a secondary Niemann-Pick type C disease-like cellular phenotype, including SLOS, as well as methods of treatment and pharmaceutical compositions. CRADA Opportunity: The National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information. Click here to view the NICHD collaborative opportunity announcement.

Novel Antigen for Use as Vaccine Against Nematode Infection

Mon, 12 Jul 2010 08:00:00 GMT
This invention describes a new vaccine against Strongyoides stercoralis, which establishes a parasitic infection that affects an estimated 100-200 million people worldwide. The potential for fatal disease associated with S. stercoralis infection and the difficulty in treating hyperinfection underscores the need for prophylactic vaccines against the disease. This vaccine uses S. stercoralis immunoreactive antigen (SsIR); a novel antigen capable of providing 70-90 % protection for mice immunized with the antigen. In addition, sera from immunized mice have also been used to effectively protect naive mice from infection.

The invention may also have potential use in diminishing allergic responses, as Strongyoides stercoralis infection has been shown to reduce the murine response to allergens. Consequently, SsIR may be used to immunize individuals and reduce the allergic response. The antigen may also be used to identify homologous antigens from other parasitic nematodes that may be important for vaccine development. CRADA Opportunity: The Laboratory of Parasitic Diseases at NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Thomas Nutman, PhD at tnutman@niaid.nih.gov or Johanna Schneider, PhD at schneiderjs@niaid.nih.gov for more information.

A Transgenic Model of Human Basal Triple Negative Breast Cancer [C3(l)-tag mice]

Mon, 12 Jul 2010 12:00:00 GMT
Basal triple-negative breast cancer (TNBC) is a common form of human breast cancer for which there are no specific, targeted therapies, unlike hormone-responsive or Her2+ breast cancers. TNBC has a much worse prognosis than hormone receptor + cancer and is disproportionately high in the African-American population. NIH scientists have created and characterized a transgenic model that is currently an excellent mouse model for TNBC that shares important molecular characteristics of human TNBC, making it highly useful for preclinical testing of drugs and novel therapies. This model may provide a valuable means of identifying new drugs and therapies that could be translated to human clinical trials. The mouse model also develops prostate intraepithelial neoplasia and prostate cancer, therefore has also been used for studies of prostate cancer. The studies using the mouse model may fill important public health service needs. CRADA Opportunity: The Transgenic Oncogenesis and Genomics Section of the Laboratory of Cancer Biology and Genetics, Center for Cancer Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this mouse model of TNBC to study cancer biology and for preclinical testing. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Use of Immunosuppressive Agents for Treatment of Age-related Macular Degeneration (AMD) and Diabetic Retinopathy

Mon, 12 Jul 2010 16:00:00 GMT
AMD belongs to a group of disorders in which the immune system may play an important role. This invention discloses that patients with AMD gain additional therapeutic benefit from combination treatment of immunosuppressive agents and standard-of-care in comparison to standard-of-care alone. This invention slows the progression of choroidal neovascularization (CNV) and may have implications for related pathologies, including diabetic retinopathy. Clinical data from a small, randomized pilot clinical trial are available. CRADA Opportunity: The National Eye Institute, Laboratory of Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of immunosuppressive agents in the treatment of age related macular degeneration. This is in light of new findings that immune mechanisms appear to be central to the expression of the clinical disease we know as AMD. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Human Single-domain Antibodies (dAbs) Against Insulin-like Growth Factor 1 Receptor (IGF-1R) and Its Ligands

Fri, 02 Jul 2010 20:00:00 GMT
Insulin-like growth factor (IGF) mediated signaling has been implicated in the development of several epithelial cancers, such as prostate, breast, and colorectal cancers. This technology consists of human single domain antibodies (dAbs) that bind to human insulin-like growth factor 1 receptor (IGF-1R) or its ligands, IGF-1 and IGF-2. These dAbs are comprised of only a single variable domain of an antibody with a human framework and three complementarity determining regions (CDRs). Several of these antibodies inhibit the IGF signaling pathway so they may be therapeutic candidates for the treatment of IGF-related cancers. CRADA Opportunity: The Center for Cancer Research Nanobiology Program (CCRNP), National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the dAbs that exhibit potent inhibitory activities against the human IGF signaling pathway. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Identification of Cancer Stem Cells

Sat, 03 Jul 2010 00:00:00 GMT
Cancer stem cells (CSC) are thought to be responsible for cancer initiation, maintenance, and therapeutic failure. A hallmark of stem cells is self-renewal via asymmetric cell division (ACD) into daughter stem-cells and cells predestined for differentiation. Demonstration of fundamental stem-cell's traits such as ACD in cancers is lacking. Label retaining cells are thought to be enriched for stem-like cells. Label retaining cells are thought to be the results of either very slow cycling cells and/ or cells undergoing ACD. This invention is directed to the identification, isolation and purification of cancer stem cells by detecting asymmetrically dividing cells and/ or label retaining cells. Detection of asymmetric cell division via non-random chromosomal cosegregation (ACD-NRCC) in various human cancers defines a unique and novel class of universal cancer stem cells, and potentially suggests a novel mechanism of carcinogenesis. The isolation of CSC might be used as a basis for a potential new strategy in cancer therapeutics. The invention also might have some implications in genetics and regenerative medicine. CRADA Opportunity: The Center for Cancer Research, Surgery Branch, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize our unique method for isolating cancer stem cells. We are seeking interested parties who would be interested in collaboration with the goal of developing cancer stem cell cell-lines for personalized targeted therapies, drug testing and finding novel targets for cancer treatments. In addition, we would like to collaborate with parties interested in developing normal (not cancer) adult tissue stem-cell cell-lines for adult tissue regeneration such as Parkinson's disease, liver failure, Alzheimer, etc. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

A New Class of Antibiotics: Naturally-occurring Chrysophaetins and Their Analogues

Mon, 21 Jun 2010 04:00:00 GMT
This invention, offered for licensing and commercial development, relates to a new class of naturally occurring antimicrobial compounds called Chrysophaetins, and to their synthetic analogues. Isolated from an alga species, the mechanism of action of these compounds is through the inhibition of bacterial cytoskeletal protein FtsZ, an enzyme necessary for the replication of bacteria. FtsZ is responsible for Z-ring assembly in bacteria, which leads to bacterial cell division. Highly conserved among all bacteria, FtsZ is a very attractive antimicrobial target.

The chrysophaetin exhibits antimicrobial activity against drug resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), as well as other drug susceptible strains. The general structure of the natural compound is shown below:

The inventors are working on a synthetic route for the compound and analogs. They have made progress and now have two halves of the molecule. These will be further dimerized to produce a synthetic chrysophaentin. It is expected that the analogues will show similar antimicrobial activity to the natural products and will utilize the same mechanism of action.

The market potential for the disclosed compounds is huge ($24 billion in 2008) due to the very limited number of new antibiotics developed in recent decades and the increased epidemic of infectious diseases. In fact, infectious diseases are the leading cause of death worldwide. In the United States alone, more people die from MRSA than from HIV (Journal of the American Medical Association, 2007) and more than 90,000 people die each year from hospital acquired bacterial infections (Centers for Disease Control). A development of new drugs with distinct mechanism of action and efficacy against resistant bacterial strains may therefore be commercially attractive. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the chrysophaentin antibiotics. Please contact Marguerite J. Miller at 301-451-3636 or millermarg@niddk.nih.gov for more information.

A Highly Sensitive ELISA for Detection of Serum Levels of Soluble IL-15 Receptor Alpha

Tue, 01 Jun 2010 08:00:00 GMT
The invention is an ELISA based assay that can be used in the clinical setting to detect the presence of soluble human IL-15 receptor (IL-15R) in the serum or plasma.

Interleukin-15 (IL-15), a cytokine has potential as an immunotherapeutic agent for cancer treatment because it is a critical factor for the proliferation and activation of natural killer (NK) and CD8+ T-cells.

In addition to studies directed toward augmenting IL-15 action to increase patient immune responses to their tumor, IL-15R alpha play a pathogenic role in leukemia and autoimmune disorders. IL-15 and IL-15R alpha are coexpressed in association with a number of autoimmune disorders including rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, chronic liver disease, and refractory celiac syndrome including that disease associated with the development of enteropathy associated CD8 T-cell lymphoma. An assay for the released serum form of IL-15R alpha is required to evaluate these IL-15R alpha inducing agents. CRADA Opportunity: The Center for Cancer Research, Metabolism Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Parkin and PINK1-Based Therapies for Parkinson's Disease and Other Mitochondrial Diseases

Tue, 01 Jun 2010 12:00:00 GMT
This technology provides methods for treating Parkinson's disease and other diseases associated with mitochondrial dysfunction.

Mutations in mitochondrial DNA (mtDNA) are responsible for a broad spectrum of inherited diseases, with symptoms that can range from mild to very severe. Accumulated mutations in mtDNA have also been linked to the pathogenesis of common diseases such as cancer, diabetes mellitus, and neurodegenerative disorders. In Parkinson's disease, for example, the accumulation of defective mitochondria appears to be responsible for the loss of midbrain neurons that produce dopamine neurotransmitter, which is a key feature of this disease.

In their recent work, Dr. Richard Youle and co-investigators have linked the fields of mitochondrial quality control and the genetics of Parkinson's disease. They have discovered that the Parkin protein is selectively recruited to damaged mitochondria, and promotes autophagic degradation of these mitochondria; ablation of Parkin increases levels of damaged mitochondria in cells. They have also discovered that another protein associated with mitochondrial disease, the mitochondrial PTEN-induced kinase-1 (PINK1), accumulates on the surface on damaged mitochondria, and that the presence of full-length PINK1 is necessary and sufficient for Parkin recruitment to the mitochondria. Thus, both Parkin and PINK1 play specific and important roles in mitochondrial quality control and disposal.

This technology describes methods of treating Parkinson's disease or other mitochondrial diseases such as KSS (Kearns Sayre syndrome), MERRF (Myoclonus epilepsy ragged-red fibers), MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes), NARP (Neuropathy ataxia, retinitis pigmentosa), and LHON (Leber hereditary optic neuropathy) by increasing PINK1 or Parkin expression or activity, as well as methods of reducing the number of defective mitochondria in a cell by increasing PINK1 or Parkin expression or activity. CRADA Opportunity: The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of treating mitochondrial diseases by increasing PINK1 or Parkin expression or activity. Please contact Dr. Martha Lubet at 301-435-3120 or lubetm@mail.nih.gov for more information.

Improving the Therapeutic Effectiveness of Foreign Proteins

Tue, 01 Jun 2010 16:00:00 GMT
Foreign proteins are recognized by the immune system, which typically responds by creating neutralizing antibodies to the foreign protein. While this is helpful in response to an infection or the administration of a vaccine, it is troublesome when foreign proteins are administered for the treatment of disease in a non-vaccine capacity (e.g., an immunotoxin, therapeutic antibody, protein replacement therapy, etc.). These neutralizing antibodies decrease the therapeutic effectiveness of the protein, ultimately resulting in the inability to administer the foreign protein to a patient with any benefit. Thus, if a particular disease requires multiple administrations, the chance of achieving a successful response with the foreign protein becomes unlikely.

A particular instance where neutralizing antibodies have reduced therapeutic effectiveness is the use of immunotoxins for treatment of cancer. Immunotoxins comprise an antibody domain for targeting a surface antigen on a cancer cell and a toxin domain that is capable of killing the targeted cell. The toxin domain is typically a modified form of a bacterial toxin, such as Pseudomonas exotoxin A, and is therefore recognized as a foreign protein by the patient's immune system. Although immunotoxins have an initial therapeutic effect, the effectiveness is ultimately mitigated by neutralizing antibodies against the toxin domain of the immunotoxin. Thus there is a clear need to reduce the formation of neutralizing antibodies in patients who are administered a foreign protein like an immunotoxin.

This technology addresses this need by reducing the formation of neutralizing antibodies through the co-administration of the immunosuppressive agent CP-690,550 with a therapeutic foreign protein. Specifically, the inventors found that co-administering CP-690,550 and an immunotoxin to a mouse model reduced the production of neutralizing antibodies to the immunotoxin. These results suggest that the use of CP-690,550 in combination with any foreign protein therapeutic could allow multiple cycles of therapy and result in improved therapeutic efficacy. CRADA Opportunity: The Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Software System for Analysis of Extremely Large Experimental Dataset and Multidimensional Drug Discovery

Tue, 01 Jun 2010 20:00:00 GMT
This invention is a computer software suite that will enable its user to investigate extremely large experimental datasets in a simple yet multidimensional manner. The software, Omnimorph, allows multidimensional investigation of any form of data including experimental datasets in biomedical science using either gene arrays or proteomics. Omnimorph allows the user to look for extremely subtle correlated differences between experimental datasets which will allow the investigator to discover far more drug- or disease-specific factors than other analytical methods currently used. The software of present invention has been employed in the targeted discovery of G protein-independent receptor-based pharmacotherapeutics. These discoveries represent an entirely new GPCR-based G protein-independent pharmacopeia. Therefore, the Omnimorph is not only newly developed software, but the Omnimorph suite can also be used as a simple and unbiased tool to detect novel and unexpected modes of GPCR-based drug actions. This could potentially alter the way drugs are developed and screened in the future. CRADA Opportunity: The National Institute on Aging, Laboratory of Neurosciences-Receptor Pharmacology Unit, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Vio Conley at 301-435-2031 or conleyv@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Delivery of Transthyretin (TTR) across the Blood Brain Barrier as a Treatment for Alzheimer's Disease

Thu, 27 May 2010 00:00:00 GMT
The invention describes products and methods of treating Alzheimer's disease. Alzheimer's disease is characterized by the formation of amyloid plaques and tangles in areas of the brain critical for learning and memory. The products are a transthyretin and other blood brain barrier impermeable proteins transformed into blood brain barrier permeable forms by the coupling of an Inter-Cellular Adhesion Molecule-1 (ICAM-1) targeting agent. Transthyretin binds to, and inhibits amyloid protein from forming plaque deposits. Deposition of amyloid is thought to underlie the disease pathology of Alzheimer's. Thus, this invention treats Alzheimer's by inhibiting the formation of amyloid plaques, which normally would result in amyloid plaque formation, inflammation, and neuronal cell death. CRADA Opportunity: The NIH Chemical Genomics Center (NCGC) is open to collaborating in order to further develop this invention. Please contact Dr. Juan Marugan at maruganj@mail.nih.gov for more information about collaborative research opportunities.

UOK171, A Spontaneous Clear Cell Type Renal Cell Carcinoma (ccRCC) Human Cell Line Derived from a Surgically Removed Tumor

Wed, 26 May 2010 04:00:00 GMT
Scientists at the National Institutes of Health (NIH) have developed a renal cell carcinoma (RCC) cell line designated UOK171 from the resected tumor of a patient diagnosed with stage IV high nuclear grade clear cell type renal cell carcinoma (ccRCC). The UOK171 cell line was immortalized spontaneously by mincing the resected tumor into pieces followed by propagation of the cells over more than twenty generations. One of the most prominent characteristics of this cell line is its intact, nonmutated von Hippel-Lindau (VHL) tumor suppressor gene. In the majority of sporadic and hereditary ccRCC cases, the VHL gene is functionally disrupted due to hypermethylation or the gene is completely lost. Thus, the UOK171 cell line is very useful as a positive control for VHL gene expression in studies of the genetic and molecular mechanisms underlying advanced ccRCC, a disease for which there is no effective treatment. Specifically, this cell line has been used as a non-methylated control cell line in studying the effects of 5-Aza-dCyd and Zebularine on VHL re-expression from methylated-VHL cell line models. These agents do not affect the methylation status of the VHL gene in UOK171. This cell line also exhibits decreased fibroblast growth factor 5 (FGF5) expression, unbalanced chromosome 3 translocations, translocations involving chromosome 14, the losses of chromosome 14 and 22, and chromosome structural aberration 1(8) (q10). UOK171 is also one of the 40-member cell lines in the National Cancer Institute (NCI) Urologic Oncology Branch (UOB) Tumor Cell Line Repository. CRADA Opportunity: The Urologic Oncology Branch, Center for Cancer Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize UOK171. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

888-mel: A Target for Anti-Tumor Immune Responses

Wed, 26 May 2010 08:00:00 GMT
Scientists at the National Institutes of Health (NIH) have developed a human melanoma cell line designated 888-mel from the resected tumor of a 26-year old Caucasian female (patient 888) diagnosed with metastatic melanoma, a frequently terminal cancer. The 888-mel cell line was derived from three separate subcutaneous melanoma lesions on the patient and possesses many characteristics representative of melanoma cell lines developed by these researchers. Most prominently, the 888-mel cell line was used to develop a tumor infiltrating lymphocyte (TIL) culture with high affinity for the tumor cells of patient 888. When the TIL 888 culture was provided as an autologous adoptive immunotherapy treatment to patient 888 in combination with interleukin-2 (IL-2), a complete remission of subcutaneous, lung, and mucosal metastases was observed in the patient for over three years.

Since this medical breakthrough, the 888-mel cell line has been well characterized through various laboratory procedures and data involving this cell line has been published as part of numerous articles. Studies have shown that the cell line expresses a variety of tumor associated antigens (TAAs), including tyrosinase, TRP1, TRP2, gp100, MART-1, p15, gp75, mutated beta-catenin, and p53. However, 888-mel does not normally express the MAGE 1, 2, or 3 TAAs. Many melanoma cell lines are HLA-A2 restricted, but the 888-mel cell line is HLA-A2 negative. The HLA class I typing for this cell line is as follows: HLA-A0101, A2402, B55, B62, Cw5201, Cw55, DRbl*1502, DRbl*1610, DQbl*0601, DRb5*0102, DRb5*0203. 888-mel is a validated source of HLA class I peptides utilized in screens that test the reactivity of TIL cultures that are candidates for adoptive immunotherapy trials. 888-mel is also a standard cell line for studying immune responses in cancer, particularly T cell responses. Other experiments show that roscovitine, a cyclin-dependent kinase inhibitor, can induce apoptosis in the 888-mel cell line, so these cells may be useful in various cell death studies. CRADA Opportunity: The Surgery Branch, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to carry out genotypic as well as phenotypic analysis of the 888 mel cell line in order to better understand the nature of tumor cells that respond to therapy. In addition, this cell line can be used as a target of humoral or cell mediated immune responses as a part of studies characterizing the nature of immune responses directed against tumor cells. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Software System for Processing and Analysis of Multi-dimensional NMR Data

Fri, 21 May 2010 12:00:00 GMT
Available for licensing is a software system useful in applications involving nuclear magnetic resonance (NMR). The software system, called NMRPipe, is written in the C programming language, and makes use of the TCL/TK scripting environment. The system includes over 500 modules for processing and analyzing experimental data of one to four dimensions collected on NMR spectrometers. The system exploits the UNIX computer operating system facilities of pipelines and scripts to link modules in a highly flexible, user-definable manner. NMR is a widely used analytical method, applied to both solution and solid state samples. The information obtained from such data pertains to the structure, motion, and interactions of molecular systems, including proteins, nucleic acids, and organic molecules. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the NMRPipe software system. Please contact Cindy Fuchs at 301-451-3636 or Frank Delaglio at frankde@niddk.nih.gov for more information.

Simple, Quantitative Sensitive High-throughput Antibody Detection for Lyme Disease

Fri, 21 May 2010 16:00:00 GMT
This technology is for compositions and methods for diagnosis of Lyme disease. Currently, Lyme disease is diagnosed by clinical exam and a history of exposure to endemic regions. Although, laboratory tests may aid diagnosis, the best tests currently available are slow and labor intensive and require understanding of the test, and infection stage. A two-step antibody based test process is currently the recommended laboratory test. The first step is either an enzyme immunoassay (EIA), or an indirect immunofluorescence assay (IFA). If the first step is positive, a “Western blot” test is then performed. Because early intervention is critical to prevent neurological, rheumatological and cardiac damage from advanced infection, more sensitive, specific, simpler, high-throughput format laboratory diagnostics are needed. This technology uses a novel synthetic gene (VOVO) in a highly sensitive, specific and high-throughput Luciferase Immunoprecipitation Systems (LIPS) format. LIPS screening using VOVO offers an efficient and qualitative approach for serological screening of antibodies in Lyme disease in human and veterinary applications. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Laboratory of Sensory Biology, Neurobiology and Pain Therapeutics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov.

The First Birt-Hogg-Dubé Tumor Cell Line and Wild Type Folliculin-restored Renal Cell Line as In Vitro and In Vivo Models

Fri, 21 May 2010 20:00:00 GMT
Scientists at the National Institutes of Health (NIH) have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dubé (BHD) syndrome and companion cell line UOK257-2 in which folliculin (FLCN) expression has been restored by lentivirus infection. These cell lines harbors a germline mutation of FLCN gene (alias BHD) and displays loss of heterozygosity, can grow as xenograft in nude mice. Patients affected with BHD develop skin papules (fibrofolliculomas), lung cysts, spontaneous pneumothorax and an increased risk for bilateral multifocal renal tumors. Loss of both copies of the FLCN gene has been documented in BHD renal tumors; however, the molecular mechanisms by which inactivation of the encoded protein, folliculin, leads to the BHD phenotype are currently unknown. They have developed an important research tool for in vitro folliculin functional studies. The companion cell line will be extremely useful for comparative biochemical analyses of cell culture systems in which the FLCN gene is either expressed or inactivated, including identification of renal tumor biomarkers, alteration of biochemical pathways resulting from loss of FLCN function, tumorigenicity of FLCN null versus FLCN restored cells, preclinical therapeutic drug testing in xenograft animal models produced from injection of these cell lines, etc. UOK 257 and UOK257-2 are thus useful cell models for studying the underlying molecular derangements associated with mTOR pathways and other biogenesis pathways in human kidney cancer and for evaluating novel therapeutic approaches for this disease. UOK257 is also one of the 40-member renal cancer cell lines in the Tumor Cell Line Repository of the Urologic Oncology Branch (UOB), National Cancer Institute (NCI). CRADA Opportunity: The Center for Cancer Research, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize kidney cancer tumor cell lines as described in above abstract through MTA, CRADAs, CTAs, BML, etc.:

For laboratory interests on the basis of metazoan tumor cell survival, including growth factor-regulated nutrient uptake; glucose or glutamine metabolism and epigenetic gene control; tumor cell bioenergetics and cell growth through AMPK and mTOR signaling pathways.

In vitro and in vivo cell model for BHD cancer syndrome. It is voluble research tool for laboratory interested in identification of new BHD tumor antigens for immunotherapy.

These paired cell lines for FLCN gene expression and function studies, including gene therapy, cytogenetics, gene mutation research, and examination abnormalities of interaction with other proteins that may contribute to BHD.

The excellent in vivo model for preclinical xenograft imaging, including stable transfection. Cells could be labeled with reagents for PET, Luciferase, Fluorescent, for transgenic mice, optical molecular imaging, etc., and provides useful platform for preclinical drug evaluations.

Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Parvovirus B19 Codon Optimized Structural Proteins for Vaccine and Diagnostic Applications

Fri, 07 May 2010 00:00:00 GMT
Parvovirus B19 (B19V) is the only known pathogenic human parvovirus. Infection by this viral pathogen can cause transient aplastic crisis in individuals with high red cell turnover, pure red cell aplasia in immunosuppressed patients, and hydrops fetalis during pregnancy. In children, B19V most commonly causes erythema infectiosum, or fifth's disease. Infection can also cause arthropathy and arthralgia. The virus is very erythrotropic, targeting human erythroid (red blood) progenitors found in the blood, bone marrow, and fetal liver. Currently, there are no approved vaccines or antiviral drugs for the treatment or prevention of B19V infection.

The subject technology is a series of plasmid constructs with codon optimized B19 viral capsid genes (VP1 and VP2) that can be expressed in mammalian cells. Transfection of vectors encoding these optimized VP1 and VP2 genes into different mammalian cell lines, including 293, Cos7, and Hela cells produce virus-like particles (VLPs). The vectors include bicistronic plasmids expressing the VP1 and VP2 proteins at different ratios to produce B19V VLPs with optimal antigenicity for vaccine applications. This technology can also be used for diagnostic applications and development of a viral packaging system for producing infectious B19V virus. CRADA Opportunity: The National Heart Lung and Blood Institute, Hematology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the subject technology. Please contact Cecilia Pazman, Ph.D., at pazmance@mail.nih.gov for more information.

Erythroid Progenitor Cell Line for Hematological Disease Applications

Wed, 05 May 2010 04:00:00 GMT
Plasmodium vivax (malaria) is a significant health concern in many parts of Asia, Latin America, North Africa, and the Middle East. There is a lack of continuous culture systems for this pathogen. The subject technology is an erythroid progenitor continuous cell line (termed CD36E) identified by erythroid markers CD36, CD33, CD44, CD71, CD235, and globoside. These CD36E cells are heterozygous for Fya and Fyb (Duffy antigen). Due to recent evidence that Plasmodium vivax (P. vivax) can infect erythroid progenitor cells (reference: YX Ru et al. and T Panichakul et al.), these cells can be potentially used for culturing P. vivax and other species of malaria. This in turn could aid development of malaria related treatments and/or products. In addition, the cell line can also be used for other hematological disease applications that involve red blood cells or red blood cell precursors. The CD36E cells also produce alpha, beta, and chi hemoglobin and therefore may be used for research involving hemoglobin. CRADA Opportunity: The National Heart Lung and Blood Institute, Hematology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the CD36E cell line. Please contact Cecilia Pazman, Ph.D., at pazmance@mail.nih.gov for more information.

Laser Scanning Microscopy for Three Dimensional Motion Tracking for Volumetric Data

Tue, 27 Apr 2010 08:00:00 GMT
The technology offered for licensing and for further development is in the field of volumetric tissue scanning microscopy. More specifically, the invention provides for a device, system and methods that can acquire and analyze volumetric data from a high-speed laser-scanning microscope and compute motion of the sample under the microscope in three dimensions. This computed motion is used to adjust position of the sample in real time to maintain field of view and relative location. This motion compensation scheme can be used to collect micron-scale information over time, which can be important in a number of research or medical device applications. CRADA Opportunity: The National Heart, Lung, and Blood Institute, Laboratory of Cardiac Energetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize automatic 3D volumetric motion tracking systems for use during in vivo microscopy. Please contact Denise Crooks, Ph.D. at 301-435-0103 or crooksd@nhlbi.nih.gov for more information.

A Method of Measuring Ultraviolet A (UVA) Protection in Sunscreen Products

Tue, 27 Apr 2010 12:00:00 GMT
There are different types of ultraviolet (UV) rays in sunlight. UVB radiation causes redness (erythema) or sunburn. While UVA radiation, which absorbs deep into the skin, causes more long-term effects such as wrinkles, skin aging and skin cancer.

Effective sunscreens are expected to block both UVA and UVB radiation. The Sun Protection Factor (SPF) label found on all over-the-counter sunscreen products is a better measure for UVB protection than UVA protection. Currently, there is no standard in vivo test to determine the amount of UVA protection in sunscreen products, despite the fact that many products are advertised as effectively blocking both UVA and UVB radiation.

This invention describes sets of genes useful for measuring UVA exposure in human skin and assessing sunscreen products for their ability to block UVA radiation. CRADA Opportunity: The Center for Cancer Research, Dermatology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Retroviral Vectors for Selective Reversible Immortalization of Stimulus-responding Primary Cells

Tue, 27 Apr 2010 16:00:00 GMT
Researchers at the National Cancer Institute-Frederick, NIH, have developed a novel set of retroviral vectors and producer cell lines useful for selective reversible immortalization of primary cells (i.e. lymphocytes) that respond to a stimulus, such as a viral antigen (e.g. HIV toxoids), a tumor antigen, or a growth factor.

Derived from the murine leukemia virus (MuLV), these retroviral vectors will only infect dividing cells. Therefore, only primary cells activated by the stimulus will be infected and immortalized, thereby creating an "antigen-specific trap."

The primary cells to be immortalized can be in targeted tissue or in stimulated ex vivo culture. The transduced cells can be expanded to large numbers without differentiating, and returned to the primary cell stage by removal of the introduced genes using a vector excision strategy. CRADA Opportunity: The Center for Cancer Research, AIDS and Cancer Virus Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Fully-human Monoclonal Antibodies Against Human EphrinB2 and EphB4 for Use in the Study of Cancer Pathogenesis

Tue, 20 Apr 2010 20:00:00 GMT
Ephrin receptor tyrosine kinases and their ephrin ligands have been implicated in cancer pathogenesis. Ephrin receptors and ligands affect tumor growth, invasiveness, angiogenesis, and metastasis. Ephrin signaling activities in cancer are complex and are only now beginning to be uncovered.

Researchers at the National Cancer Institute-Frederick, NIH, have developed a set of five fully-human monoclonal antibodies against human Ephrin-B2 and Ephrin type-B receptor 4 ("EphB4"). The antibodies were identified by screening a naïve human antibody phage display library against Ephrin-B2 and EphB4. These human monoclonal antibodies have high affinity and specificity for Ephrin-B2 and EphB4. CRADA Opportunity: The Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

15kD Granulysin for Monocyte Differentiation: A New Immunotherapeutic for Both in vivo and ex vivo Applications

Wed, 21 Apr 2010 00:00:00 GMT
Granulysin is a cytolytic and proinflammatory molecule expressed by activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It has been implicated in many of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Small synthetic forms of granulysin are being developed as novel antibiotics and studies suggest that granulysin may be a useful diagnostic biomarker and/or therapeutic for a wide variety of diseases.

The invention relates to methods of stimulating or enhancing an immune response using 15 kD granulysin. Investigators at the NIH have discovered that 15 kD granulysin (but not 9 kD granulysin) activates monocytes and induces them to differentiate into mature dendritic cells and activates allospecific T cells. This activation and subsequent differentiation induced by 15 kD granulysin may prove important in inducing or regulating immune responses in a host. Consequently, this invention could be used treat tumors and infections, particularly as an adjuvant for vaccines and immunotherapies. Further, this technology could be used to treat autoimmune disorders and organ transplant rejection. CRADA Opportunity: The Center for Cancer Research, Laboratory of Cellular and Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3131 or hewesj@mail.nih.gov for more information.

Thermostable Y-Family Polymerases From Fungi for Use in Forensic DNA Services and Analysis of Damaged or Ancient DNA

Tue, 20 Apr 2010 04:00:00 GMT
Y-family polymerases are able to bypass lesions in DNA that would otherwise block replication by high fidelity DNA polymerases and are key to the effective study of ancient DNA and for use in forensic medicine. These enzymes are ubiquitous and are found in all kingdoms of life: bacteria, archaea and eukaryotes. The number of proteins related to the Y-family polymerases is well over 200 orthologs and despite being closely related at the phylogenetic level, the few polymerases now characterized, each show a unique set of properties including processivity, fidelity, and the ability to bypass certain types of DNA. Y-family polymerases from thermostable organisms are of particular interest because the enzymes isolated from such species tend to be more stable, easy to work with and may have more utility in assays at higher temperatures, such as Polymerase Chain Reaction (PCR). For example, the thermostable archeal Sulfolobus solfataricus DinB-like polymerase Dpo4 can bypass lesions by generally inserting the correct complementary nucleotide opposite a variety of damaged bases and can, under appropriate conditions substitute for Taq polymerase in PCR applications [Nucleic Acids Res. 2001 Nov 15;29(22):4607-4616; HHS Ref. No. E-232-2001/0]. Additionally, functional and structural organization of this family of polymerases permits domain swapping designed to optimize specific properties of use in novel applications [J Biol Chem. 2004 Jul 30;279(31):32932-32940].

Dr. Woodgate's group at the National Institute of Child Health and Development have expanded their earlier work (HHS Ref. Nos. E-166-2004/0, /1, & / 2) and have now cloned and expressed full length Y-family polymerases Thermoascus auranticus Pol eta, Thermomyces lanuginosus Pol eta, Thermomyces lanuginosus Pol iota, Thermomyces lanuginosus Pol kappa, Thermomyces lanuginosus REV1, Sporotrichum thermophile Pol eta, Sporotrichum thermophile Pol iota, Sporotrichum thermophile Pol kappa, and Sporotrichum thermophile REV1. These full length enzymes may be a good substitute for Taq polymerase in applications utilizing fluorescent nucleoside triphosphate derivatives. These lesion-bypassing polymerases could also be included along with a conventional thermostable polymerase in a PCR protocol designed to amplify old or damaged DNA samples which could greatly increase recoverability, accuracy and length of products. Other applications could include labelling or tagging DNA, real-time PCR, detection of SNPs, mismatches or DNA lesions, mutagenic PCR, directed-evolution methods and expanding the "DNA alphabet" utilizing non-natural nucleotides.

Available for licensing are several full length novel Y-family polymerases. These enzymes and methods should be of interest to forensic DNA service companies as well as to research reagent companies pursuing novel thermophilic enzymes for use in ancient and damaged DNA analysis and for novel applications with modified nucleotides. CRADA Opportunity: The National Institute of Child Health and Human Development, Laboratory of Genomic Integrity, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the aforementioned thermostable fungal Y-family DNA polymerases. Please contact Joseph Conrad, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information. Click here to view the NICHD collaborative opportunity announcement.

Nontypeable Haemophilus Influenzae Lipooligosaccharide Based Conjugate Vaccines for the Prevention of Otitis Media and Respiratory Infections

Tue, 20 Apr 2010 08:00:00 GMT
Nontypeable Haemophilus influenzae is one of the leading causative agents of otitis media in children and accounts for 11% of pneumonia cases in children. This is due in part to the current immunizations of children with Streptococcus pneumoniae polysaccharide and conjugate vaccines to prevent otitis media. The proportion of otitis media caused by pneumococcal strains covered by the vaccines have decreased while those caused by nontypeable Haemophilus influenzae have significantly increased. At some point during early childhood, otitis media affects more than 80% of children under 6 years of age. Otitis media can lead to deafness and language or learning deficits. In adults, nontypeable Haemophilus influenzae causes respiratory tract infections primarily in persons with chronic obstructive pulmonary disease, one of the most common lung diseases. Exacerbation of chronic obstructive pulmonary disease in the elderly is the fourth leading cause of death in the United States. Otitis media can be treated with antibiotics; however, the emergence of antibiotic resistance makes vaccines against nontypeable Haemophilus influenzae an attractive alternative to those classes of drugs. The current Haemophilus influenzae type b conjugate vaccines have no protective effect against nontypeable strains.

The technologies described herein are conjugate vaccines against nontypeable Haemophilus influenzae. The vaccines are comprised of lipooligosaccharides (LOS) from which esterified fatty acids have been removed from lipid A to form detoxified LOS conjugated to an immunogenic carrier such as tetanus toxoid, and an adjuvant such as alum. In vivo data in the Chinchilla animal model are available. The vaccines can be potentially used as a component in a combination vaccine with other pediatric vaccine components. CRADA Opportunity: The National Institute on Deafness and Other Communication Disorders, Vaccine Research Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the subject technology. Please contact Brian W. Bailey, Ph.D. at 301-594-4094 or bbailey@mail.nih.gov for more information.

Moraxella Catarrhalis Lipooligosaccharide Based Conjugate Vaccines for the Prevention of Otitis Media and Respiratory Infections

Tue, 20 Apr 2010 12:00:00 GMT
Moraxella catarrhalis is one of the three leading causative agents of otitis media in children. This is due in part to the current immunizations of children with Streptococcus pneumoniae polysaccharide and conjugate vaccines to prevent otitis media. The proportion of otitis media caused by pneumococcal strains covered by the vaccines have decreased while those caused by Moraxella catarrhalis and nontypeable Haemophilus influenzae have significantly increased. At some point during early childhood, otitis media affects more than 80% of children under 6 years of age. Otitis media can lead to deafness and language or learning deficits. In adults, Moraxella catarrhalis is a major cause of bronchopneumonia and exacerbation of existing chronic obstructive pulmonary disease for chronic heavy smokers or elderly patients with chronic pulmonary disease. Moraxella catarrhalis infections can be treated with antimicrobial agents; however, the emergence of antibiotic resistance makes vaccines against Moraxella catarrhalis an attractive alternative to antimicrobial drugs. There are currently no Moraxella catarrhalis vaccines on the market.

The subject technologies are conjugate vaccines against Moraxella catarrhalis. The vaccines are comprised of isolated lipooligosaccharides (LOS) from which esterified fatty acids have been removed to produce detoxified LOS or from which lipid A has been removed to produced a detoxified oligosaccharide (OS) covalently linked to an immunogenic carrier such as tetanus toxoid, and adjuvants such as alum. The vaccines can potentially be used as a vaccine component in a combination vaccine containing other pediatric vaccine components. CRADA Opportunity: The National Institute on Deafness and Other Communication Disorders, Vaccine Research Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the subject technology. Please contact Brian W. Bailey, Ph.D. at 301-594-4094 or bbailey@mail.nih.gov for more information.

A Method of Reducing Cholesterol Biosynthesis with Specific MicroRNAs

Tue, 20 Apr 2010 16:00:00 GMT
This technology is directed to the discovery of specific microRNAs that target and downregulate enzymes within the cholesterol biosynthetic pathway and is currently being tested in vivo.

Briefly, microRNAs regulate the translation of messenger RNAs (mRNAs) into protein. The inventors have discovered a set of specific microRNAs that downregulate the expression of multiple enzymes in the cholesterol biosynthetic pathway. Importantly, this technology may provide the benefits of cholesterol lowering therapies to patients that are not suited for statin-based treatments. Statins block the cholesterol biosynthetic pathway at a single enzymatic step and may result in the deleterious build-up of a metabolic intermediate. In contrast, this technology simultaneously targets the expression of multiple enzymes required for cholesterol biosynthesis and thus may avoid the build-up of metabolic intermediates. The reduction of cholesterol biosynthesis has been indicated for improved cardiovascular health and lowers the risk for heart disease, heart attack, and stroke. CRADA Opportunity: The National Heart, Lung and Blood Institute, Pulmonary Vascular Medicine Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize microRNA regulation of the cholesterol biosynthetic pathway. Please contact Dr. Denise M. Crooks at 301-435-0103, crooksd@nhlbi.nih.gov for more information.

New Mouse Strain with Conditional Deletion of SMAD7: Analysis of Disease Processes Involving Immunological, Fibrotic or Cardiovascular Indications

Tue, 20 Apr 2010 20:00:00 GMT
SMAD7 conditional knockout mice are available for licensing. SMAD7 can be knocked out by breeding with CRE-recombinase transgenic mice with a variety of promoters to yield tissue or cell type-specific deletions of SMAD7. SMAD7 has been shown to play a role in bone morphogenesis, cardiovascular tissue generation, immune regulation and fibrosis. Therefore, these mice provide a unique model to examine the role of the SMAD7 gene in disease processes that involve immunological, fibrotic, or cardiovascular components. Specifically, these mice may represent a novel model of Scleroderma, a disease with both an immunological and fibrotic component. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Dr. Elizabeth M. Denholm, denholme@niehs.nih.gov, for more information.

Topical Formulation of Histone Deacetylase (HDAC) Inhibitors: Treatments for Cancer and Immunological Skin Disorders

Wed, 21 Apr 2010 00:00:00 GMT
This technology relates to topical formulations of Histone Deacetylase (HDAC) inhibitors (HDIs) that can be used to treat cancers such as cutaneous T-cell lymphoma (CTCL) and skin disorders such as lupus, contact dermatitis, and drug eruptions which are associated with malignant or autoreactive lymphocytes from the immune system. HDIs, such as depsipeptide, have been demonstrated to be effective against CTCL when administered internally but a topical preparation may be more useful for treatment at earlier stages of the disease.

HDIs are molecules that inhibit the activity of a group of enzymes that remove small chemical groups called acetyl groups from many different proteins, including proteins that regulate gene expression. By altering the acetylation of these proteins, HDAC inhibitors can induce tumor cell differentiation, cell cycle arrest, and cell death. A variety of chemically distinct molecules exhibit HDAC inhibitory activity and their potential as therapeutics for cancer and other indications is being investigated. The HDI depsipeptide is a cyclical peptide derived from a bacterium and is indicated as a second line treatment for CTCL through intravenous administration. Development of a topical preparation of depsipeptide and/or other HDAC inhibitors may help reduce their toxicity and increase their effectiveness in treating CTCL, other cancers, as well as other diseases. CRADA Opportunity: The Center for Cancer Research, Medical Oncology Branch and Affiliates, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize topical therapy using HDIs. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Composite Probes and Use Thereof in Super Resolution Microscopy

Tue, 20 Apr 2010 04:00:00 GMT
The technology is in the field of fluorescence microscopy. More specifically, the invention describes and claims the composite probes for super resolution optical techniques using super resolution via transiently activated quenchers (STAQ). The composite probes include a donor moiety and an acceptor moiety joined by a linker. The acceptor moiety, when excited by incident radiation, is excited to a state which, for example, absorbs in the donor emission region, such that the acceptor moiety in its excited state quenches at least a portion of the donor moiety emission. Other transiently activated quenching mechanisms and moieties could accomplish the same task by reducing donor population. Also disclosed are methods for irradiating a selected region of a target material including the composite probe, wherein the composite probe enables improved resolution by point spread function modification. CRADA Opportunity: The National Heart, Lung and Blood Institute, Laboratory of Molecular Biophysics, is also seeking statements of capability or interest from parties interested in collaborative partnerships to further develop, evaluate, or commercialize this technology. Please contact Brian Bailey, Ph.D. at bbailey@mail.nih.gov for more information.

Peroxidase and Peroxidase Substrate Peptides (PSPs) for Treatment of Inflammatory Disorders and Allergies

Tue, 20 Apr 2010 08:00:00 GMT
NIH investigators have identified an unexpected and previously unrecognized function of the peroxidase/dual oxidase system in protecting the mucosal surfaces, such as in the gastrointestinal and respiratory tracts. Specifically, NIH investigators have shown that a peroxidase and a dual oxidase (Duox) form a dityrosine network that decreases gut permeability to immune elicitors and prevents activation of epithelial immunity in An. gambiae mosquitoes. This technology provides for novel compositions that enhance the formation of a dityrosine network on epithelial cells, such as those found in the gastrointestinal and respiratory tract mucosa of vertebrates, by forming a mucosal barrier on the epithelial surface preventing or inhibiting epithelial cell-mediated inflammatory responses (such as those associated with an inflammatory disease or an allergic reaction). Exemplary compositions include a mammalian or plant heme peroxidase and a peroxidase substrate peptide (PSP).

The compositions of this technology can be useful as therapeutics for several diseases or disorders involving epithelial cell-mediated inflammatory responses (e.g., inflammatory bowel diseases such as Crohn's, and allergic disorders). CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Office of Technology Development, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Peroxidase and Peroxidase Substrate Peptides (PSPs) for Treatment of Inflammatory Disorders and Allergies. Please contact Dana Hsu at 301-496-2644 for more information.

Use of Modified Peptide Nucleic Acids for Visualizing DNA

Thu, 25 Mar 2010 12:00:00 GMT
The compounds described in this technology may be useful in the development of nucleic acid detection kits for various pathogens.

Technologies for genomic detection most commonly use DNA probes to hybridize to target sequences, and require the use of Polymerase Chain Reaction (PCR) to amplify target sequences. Replacing the DNA probe with peptide nucleic acid (PNA) can greatly eliminate the need for PCR because the binding strength of PNAs to complementary DNA is stronger than DNA binding to complementary DNA. In addition, PNAs are nuclease and protease resistant, and form very stable and highly sequence-specific complexes with DNA.

This technology describes a method of making pure enantiomers of trans-tert-butyl-2-aminocyclopentylcarbamate (tcycp) and methods of modifying PNAs by incorporating tcycp compounds into the PNA. This technology may also be practical for detecting infectious agents such as anthrax, avian flu, tuberculosis (TB), severe acute respiratory syndrome (SARS), human papilloma virus (HPV) and human immunodeficiency virus (HIV). CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, Drug-Receptor Interactions Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Dr. Daniel Appella at appellad@niddk.nih.gov for more information.

Novel Compositions for Use as Bone Scaffolds and Enhancers of Bone Regeneration

Thu, 25 Mar 2010 16:00:00 GMT
This invention is directed to the discovery that a mixture of an organic polymer and inorganic particles may hold therapeutic utility as a biomaterial for artificial bone scaffolds, injectable bone-filling materials, and enhancement of new bone generation. This composition has demonstrated utility in vivo in mice.

The inventors have discovered a means of producing a stably homogenous mixture of the organic polymer and inorganic particles by crosslinking the two components. In contrast to current technologies, this invention not only imparts sufficient mechanical and load-bearing strength but also provides a suitable environment for new bone formation. Importantly, since the chemical reaction applied to make this biomaterial does not produce any harmful molecules or heat, it can be used in an injectable form. Bone formation or replacement is often a desired therapy for bone loss or defects due to fractures or bone degenerative diseases. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

Radioprotectants and Tumor Radiosensitizers Targeting Thrombospondin-1 and CD47

Thu, 25 Mar 2010 20:00:00 GMT
Radiation therapy not only damages cancer cells, but it also damages healthy cells and can cause serious side effects for patients. One effort to enhance the therapeutic potential of radiotherapy, while reducing its detrimental effects on normal tissue and maintaining tumor sensitivity, is centered upon the development of radioprotective agents.

NIH inventors previously discovered that when the secreted protein, thrombospondin-1 (TSP1) binds to its receptor CD47, this signaling pathway prevents nitric oxide from dilating blood vessels and increasing blood flow to organs and tissues. They found that blocking TSP1-CD47 interaction through the use of antisense morpholino oligonucleotides, peptides or antibodies has several therapeutic benefits; one of them being increased blood flow to ischemic tissues.

In the present technology, the inventors discovered that hindlimb irradiated TSP1 and CD47 null mice have less hair loss, and decreased cell death in muscle and bone marrow than untreated TSP1 and CD47 null mice. They also discovered that when irradiated human vascular cells are treated with antibodies towards TSP1 or CD47, viability and proliferative capacity are preserved. Furthermore, the inventors determined that irradiation of wild type mice following treatment with CD47 antisense morpholino resulted in decreased apoptosis in irradiated tissues at 24 hours, preservation of hematopoietic stem cell proliferative capacity in irradiated bone marrow, and less alopecia, ulceration, and desquamation at the end of eight weeks. These results led the inventors to propose that antagonists of TSP1 and/or CD47 preserve cell viability and tissue function following radiation treatment, and these antagonists may be useful as radioprotective agents to reduce side effects associated with radiation therapy. Remarkably, the same treatment dramatically enhanced the delay in melanoma and squamous carcinoma tumor regrowth following irradiation. Thus, these agents are radioprotective agents for normal tissue but radiosensitizers for tumor tissue.

The present technology describes the use of morpholinos, peptides and antibodies that block the TSP1/CD47 signaling pathway as radioprotectants for normal tissue, radioenhancers for tumor tissue, and methods of selectively protecting normal tissue from damage caused by radiation exposure by contacting the tissue with these agents. CRADA Opportunity: The Center for Cancer Research, Laboratory of Pathology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize CD47-targeting agents as radioprotectants and tumor sensitizers. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Zscan4, a Therapeutic Target for Cancer, Regenerative Medicine and Aging

Thu, 25 Mar 2010 00:00:00 GMT
This technology has broad potential for the development of therapeutics for cancer, diseases of aging, and regenerative medicine, and targets Zscan4, a gene that regulates telomere length and genomic stability in embryonic stem (ES) cells.

The ability to maintain genomic stability in ES cells and other stem cells is critical for the development of stem cell-based therapies; genomic stability and telomere length are also active areas of cancer and aging research. NIA investigators have discovered that the Zscan4 gene regulates telomere length and genomic stability in ES cells, and plays an essential role in early embryonic development; this activity is independent of telomerase activity. The investigators have shown that ablation of Zscan4 results in shortened telomere length and deterioration of the karyotype of ES cells, and that Zscan4 overexpression increases telomere length.

This technology discloses methods for increasing genome stability or increasing telomere length in an ES cell, and methods of treating a subject in need of ES cell therapy. Also disclosed are methods of promoting blastocyst outgrowth of embryonic stem cells, as well as Zscan4 expression vectors and methods of identifying stem cells expressing Zscan4. CRADA Opportunity: The National Institute on Aging, Laboratory of Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Nicole Guyton, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information.

Long Acting Ophthalmic Analgesic Eye Drops

Tue, 23 Mar 2010 04:00:00 GMT
This invention is directed to the discovery that resiniferatoxin (RTX) produces a three to four day analgesic effect when topically applied to the cornea. Efficacy for RTX as an effective analgesic has been demonstrated in vivo in rats. Importantly, unlike currently available analgesics, RTX left the blink reflex intact and did not impact mechanical sensitivity. RTX also did not impair epithelial wound healing and functioned without detectable damage to the cornea.

RTX is a potent agonist of the transient receptor potential channel, subfamily V, member 1 (TRPV1). TRPV1 is involved in pain sensation and is expressed only in select neurons. Unlike other local analgesics that target a wide breadth of neurons, RTX targets only those neurons that express TRPV1, leaving the important blink reflex and mechanical sensitivity of the eye unaffected. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Laboratory of Sensory Biology, Neurobiology and Pain Therapeutics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

mFPR2 Transgenic and Knockout Mouse Models for Alzheimer's and Other Inflammatory Diseases

Fri, 19 Mar 2010 08:00:00 GMT
Human Formyl Peptide-Like Receptor 1 (hFPLR1) has been implicated in host defense for disease processes including Alzheimer's disease, infection, and other inflammatory diseases. hFPLR1 and its mouse homologue Formyl Peptide Receptor 2 (mFPR2) are G-protein coupled receptors that are expressed at high levels on phagocytic leukocytes, mediating leukocyte chemotaxis and activation in response to a number of pathogen- and host-derived peptides. Activation of hFPRL1/mFPR2 by lipoxin A4 may play a role in preventing and resolving inflammation. Also, hFPRL1/mFPR2 has been shown to mediate the chemotactic activity of amyloid beta 1-42, a key pathogenic peptide in Alzheimer's disease.

Available for licensing are mice expressing the mFPR2 transgene on either the FVB or C58BL background, as well as mFPR2 knockout mice on the C57BL background. These mice are anticipated to be highly useful in the study of a wide variety of inflammatory, infectious, immunologic and neurodegenerative diseases. CRADA Opportunity: The National Cancer Institute - Frederick, Laboratory of Molecular Immunoregulation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize mFPR2 Transgenic and Knockout Mouse Models for Alzheimer's and Other Inflammatory Diseases. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Polarization Adapter for Colposcope

Wed, 17 Mar 2010 12:00:00 GMT
The invention offered for licensing is directed to a polarization adaptor for colposcopes. The colposcope is a medical diagnostic device that examines an illuminated magnified view of a patient's cervical, vaginal, and vulva tissues during a colposcopy procedure. Specifically, the invention provides for a specialized polarized camera (polarization adaptor) for integration into commercially available colposcopes. The addition of polarization to currently available colposcope results in an enhanced image video output that allows the user to view hidden subsurface tissue structures and textures, thereby allowing for better diagnosis of pathological conditions.

The device which can readily be adapted to commercial colposcope enables the separation of specularly reflected light from diffusely backscattered light, coming from deeper tissue layers. In combination with suggested data processing algorithm, based on correlation analysis, this allows one to enhance imaging of the hidden subsurface tissue structure (texture). CRADA Opportunity: The Eunice Shriver National Institute of Child Health and Human Development, Section on Analytical and Functional Biophotonics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the polarization camera for cervical tissue characterization. Please contact Joseph Conrad, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

A New Transmission Blocking Vaccine for Leishmania Infection

Wed, 17 Mar 2010 16:00:00 GMT
A novel transmission blocking vaccine has been developed that can eliminate or reduce the number of Leishmania chagasi parasites in the gut of the sand fly species, Lutzomyia longipalpis. The vaccine involves the production of antibodies to the sand fly midgut protein, LP1, which is normally expressed in the midgut of the sand fly during a blood meal. This vaccine could potentially block parasite transmission from the sand fly to mammalian hosts and significantly reduce the incidence of leishmaniasis in endemic areas of the world such as Brazil, India, and Indonesia where leishmaniasis accounts for over 58,000 deaths annually.

Studies have shown that LP1 antibodies produced by immunized mice are able to reduce the number of L. chagasi parasites that develop in the midgut of Lu. longipalpis. These results illustrate the potential use of the protein as a vaccine to immunize dogs and protect humans from visceral leishmaniasis transmitted by the sand flies that feed on the infected, vaccinated dogs. In endemic areas such as Brazil where dogs are the principal reservoir for L. chagasi, the LPl antigen alone or in combination with other sand fly midgut proteins could be used to immunize household pets and stray dogs. Vaccinated dogs will produce antibodies to LPl, and once a sand fly feeds on blood from the infected and vaccinated dogs, the antibodies will inhibit development of the parasite in the gut of the sand fly. This approach can effectively block Leishmania transmission to human hosts. Such vaccines have the potential to reduce the risk of humans acquiring leishmaniasis without the risks involved in human vaccination. CRADA Opportunity: The NIAID, OTD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize "A New Transmission Blocking Vaccine for Leishmania Infection". Please contact Dana Hsu at 301-496-2400 for more information.

Novel Regulatory B cells for Treatment of Cancer and Autoimmune Disease

Wed, 17 Mar 2010 20:00:00 GMT
The manner by which cancers evade the immune response is not well-understood. What is known is that the manner is an active process that regulates immune responses employing at least two types of suppressive cells, myeloid-derived suppressive cells and regulatory T cells (Tregs), a key subset of CD4⁺ T cells that controls peripheral tolerance to self- and allo-antigens. Tregs are considered to play a key role in the escape of cancer cells from anti-tumor effector T cells.

Cancer cells have been found to directly activate resting B cells to form suppressive regulatory B cells (tBregs) and utilize them to evade immune surveillance and mediate metastasis. tBregs directly inhibit CD4⁺ and CD8⁺ T cell activity in a cell contact-dependent manner, induce FoxP3⁺ T cell activity, and promote Treg-dependent metastasis.

Researchers from the National Institute on Aging (NIA), NIH, have developed methods for the generation of tBregs, and for using tBregs to produce Tregs, and methods that inactivate or deplete tBregs. These methods have significant therapeutic value in the combat with cancer immune escape and metastasis, and in the control of harmful autoimmune diseases. CRADA Opportunity: The Immunotherapeutics Unit, National Institute on Aging, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the utilization of regulatory B cells to control autoimmune diseases and strategies that inactivate tBregs to control cancer immune escape. Please contact Nicole Darack, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Akt-Ser473 Phosphorylation as a Marker for Predicting Taxane Chemotherapy Outcome

Fri, 12 Mar 2010 01:00:00 GMT
Over the past decades, taxanes such as paclitaxel and docetaxel have emerged as effective chemotherapy agents for breast cancer and other malignancies. Taxanes are effective in many patients, however, not all patients benefit from this type of chemotherapy. A significant need remains for a means of predicting clinical outcome from taxane-based chemotherapy.

Akt, a serine/threonine kinase that can block apoptosis, has been implicated in the regulation of microtubule dynamics and organization. Akt phosphorylation and its transducing downstream events play a central role in cell survival and cell cycle progression at the G2/M transition. Paclitaxel or docetaxel inhibits Akt-Ser473 phosphorylation (pAkt) and induces mitotic arrest. Therefore, taxanes may cause more damage to tumor cells that are dependent on pAkt for survival and cell cycle progression, significantly impacting treatment outcome.

Researchers at the National Cancer Institute, NIH, have identified pAkt as having predictive significance for paclitaxel chemotherapy outcome in patients with early stage breast cancer. The researchers have developed an immunohistochemistry method for determining pAkt status with appropriate controls for assay performance and cutoff for pAkt positivity. They also discovered methods of correlating pAkt expression with clinical outcome (disease-free survival and overall survival). pAkt is a novel predictive marker of taxane chemotherapy, and can be applied to indicate which patients should receive taxane-based chemotherapy. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the pAkt assay for use in a clinical setting. The National Cancer Institute would be particularly interested in discussing collaborations to provide additional clinical validation of pAkt as a primary biomarker. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Tumor Tissues Harboring Mutations in cAMP-specific Phosphodiesterases Useful for the Study of Endocrine Tumors

Thu, 11 Mar 2010 06:00:00 GMT
Researchers at the National Institute of Child Health and Human Development (NICHD), NIH, have made available samples of patient-derived adrenal and heart tumors that harbor genetic mutations that have been implicated in the predisposition of endocrine tumors. An endocrine tumor is a growth that affects the parts of the body that secrete hormones. Because an endocrine tumor arises from cells that produce hormones, the tumor itself can produce hormones and cause serious illness.

The tumor samples made available herein contain deletions in the cyclic nucleotide phosphodiesterase (PDE) PDE7A or PDE8B genes that impair PDE function and are characterized by high sensitivity to changes in cAMP levels. Commercially, phosphodiesterase inhibitors are widely used in the treatment of various disorders, including asthma, pulmonary hypertension, and erectile dysfunction, suggesting a potential utility for these tissues in a wide range of investigations. CRADA Opportunity: The National Institute of Child Health and Human Development, Division of Intramural Research, is seeking statements of capability or interest from parties interested in collaborative research. Please contact Joseph Conrad, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Spontaneously Transformed Mouse Epithelial Cancer Cell Lines Serving as Mouse Models: A New Model for Cancer Research

Thu, 11 Mar 2010 11:00:00 GMT
Investigators at the NIH have created a collection of 45 mouse epithelial cancer cell lines derived from six organs: bladder, cervix, colon, lung, kidney, and mammary glands. These cell lines were obtained from spontaneously transformed primary cell cultures without genetic, viral or chemical manipulation so they can serve as mouse models for studying the natural process of oncogenesis.

The cell lines were characterized cytogenetically during their transformation from normal to spontaneously immortalization and were found to recapitulate many of the changes observed in human cancer cells such as the deregulation of oncogenes (Myc, Mdm2) and tumor suppressor genes (Cdnk4a/Ink4a/p16, Rb).

Carcinomas that arise from the epithelial cells lining organs lead to the most common cancers in humans. However, research on cellular transformation has largely relied on fibroblast cells which are not of epithelial origin and therefore, may not reflect the changes that lead to epithelial oncogenesis. The availability of these mouse epithelial cancer cell lines should allow for a more accurate analysis of this process. CRADA Opportunity: The National Cancer Institute, Cancer Genetics Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Defensin-Based Therapeutics for the Treatment of Pulmonary Disease

Thu, 11 Mar 2010 16:00:00 GMT
Investigators at the National Heart, Lung and Blood Institute have developed modified defensins that are resistant to degradation, have improved characteristics compared to unmodified defensins, and are promising candidates for pulmonary disease therapeutics.

Defensins are small cationic peptides that defend the lung against pathogenic microorganisms and play an important role in innate immunity. However, during lung inflammation, defensin concentrations can reach levels that are cytotoxic for airway epithelial cells. Therefore, the development of methods to produce modified defensins that exhibit reduced cytotoxicity, while retaining the ability to stimulate the innate immune response, would be of potential therapeutic benefit for pulmonary diseases.

The inventors have previously shown that a defensin, human neutrophil peptide 1 (HNP-1), is elevated in samples from the lungs of patients with inflammatory lung disease, and that the HNP-1 in these samples is ADP-ribosylated at one or both of two arginine residues within the protein. In vitro studies by the inventors show that ADP-ribosyl-HNP-1 has reduced cytotoxic activity compared to HNP-1, while retaining its T cell chemotactic properties and ability to promote neutrophil recruitment, and thus ADP-ribosyl-HNP-1 may play an important role as a regulator of the inflammatory response. These properties would also be useful for treatment of pulmonary inflammation and lung diseases. However, ADP-ribosylated HNP-1 and other defensins are degraded rapidly in vivo due to the susceptibility of the ADP-ribose moiety to attack by hydrolases and pyrophosphatases, which limits their therapeutic potential.

The inventors have recently discovered that the ADP-ribosylated arginine residues in HNP-1 can be converted to ornithine through a non-enzymatic process that results in a peptide with an altered pharmacological profile. The investigators have also successfully generated ornithine-substituted ADP-ribosyl HNP-1 and ornithine-HNP-1 in vitro, which are currently being characterized. Thus, ornithine-substituted ADP-ribosyl HNP-1 and ornithine-HNP-1 may be promising candidates for the development of therapeutics to treat pulmonary disease, and the strategy of replacing ADP-ribosylated residues with ornithine to enhance stability and therapeutic efficacy may also be extended to other defensins.

Through an earlier, related invention, the inventors have also demonstrated that recombinant proteins wherein tryptophan or phenylalanine residues substitute for ADP-ribosylarginine have a similar stabilizing impact on polypeptides, making them more suitable as therapeutic agents.

The inventors also hypothesize that it would be possible to develop a treatment that increases levels of an ADP-ribosylated therapeutic protein, such as HNP-1, in the lung via inhalation administration of the therapeutic protein in conjunction with nicotinamide adenine dinucleotide (NAD), which is required for ADP-ribosylation. This could represent a unique therapeutic strategy for treating pulmonary disease. CRADA Opportunity: The National Heart, Lung and Blood Institute Translational Medicine Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize defensin-based therapeutic agents to treat pulmonary diseases. Please contact Brian W. Bailey, Ph.D. at 301-494-4094 or bbailey@mail.nih.gov for more information.

Caspase Inhibitors Useful for the Study of Autoimmune or Inflammatory Diseases

Thu, 11 Mar 2010 21:00:00 GMT
Novel and potent caspase 1 inhibitors are available for licensing. In particular, this technology discloses potent and selective caspase 1 inhibitors that target the active site of the enzyme. Caspase 1 is known to play a pro-inflammatory role in numerous autoimmune and inflammatory diseases and therefore represents an excellent target for treatment of a broad range of diseases, including but not limited to Huntington's, amyotrophic lateral sclerosis, ischemia, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, and sepsis. Not surprisingly this enormous potential has resulted in at least three caspase 1 inhibitors entering clinical trials (VX-740, IDN-6556, and VX-765) in recent years. CRADA Opportunity: The NIH Chemical Genomics Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize appropriate lead compounds described in U.S. Provisional Application No. 61/299,790. Please contact Dr. Craig J. Thomas via e-mail (craigt@nhgri.nih.gov) for more information.

Conditional V2 Vasopressin Receptor Mutant Mice as a Model to Study X-linked Nephrogenic Diabetes Insipidus (XNDI)

Tue, 02 Mar 2010 02:00:00 GMT
X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present, no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. This technology provides a unique and viable animal model of XNDI. NIH investigators have generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen. Radioligand-binding studies confirmed the lack of V2R-binding sites in kidneys following 4-OH-tamoxifen treatment, and further analysis indicated that upon V2R deletion, adult mice displayed all characteristic symptoms of XNDI, including polyuria, polydipsia, and resistance to the antidiuretic actions of vasopressin.

Gene expression analysis suggested that activation of renal EP4 PGE2 receptors might compensate for the lack of renal V2R activity in XNDI mice. Strikingly, both acute and chronic treatment of the mutant mice with a selective EP4 receptor agonist greatly reduced all major manifestations of XNDI, including changes in renal morphology. These physiological improvements were most likely due to a direct action on EP4 receptors expressed on collecting duct cells. These findings illustrate the usefulness of V2R mutant mice for elucidating and testing new strategies for the potential treatment of humans with XNDI. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, Molecular Signalling Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Dr. Jurgen Wess at jwess@helix.nih.gov for more information.

A Biomarker and Therapeutic Target for Ovarian Cancer

Mon, 01 Mar 2010 07:00:00 GMT
This technology provides methods of diagnosing or treating certain ovarian cancers using STAMP, a steroid cofactor. There are currently no effective methods for early-stage diagnosis of ovarian cancer. Diagnosis is usually made through a combination of physical examination, ultrasound imaging, and a blood test for the tumor marker CA-125. The CA-125 test only returns a true positive result for about 50% of early-stage ovarian cancers, and may be elevated in other conditions not related to cancer, so it is not an adequate early detection tool when used alone.

The inventors have shown that STAMP mRNA levels are elevated in ovarian cancer samples, including early-stage cancers. They have also found that in a subset of ovarian cancer cell lines, introduction of STAMP siRNAs slows cell proliferation. These findings suggest that STAMP may be useful as a biomarker to detect early stage cancer in ovarian tissues, and is also promising as a therapeutic target for a subset of ovarian cancers. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Steroid Hormones Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize STAMP, a steroid cofactor. Please contact Dr. S. Stoney Simons at steroids@helix.nih.gov for more information.

Diagnosis and Treatment of Cancer Using Histone Deacetylase Inhibitors and Radiolabeled Metaiodobenzylguanidine

Mon, 01 Mar 2010 12:00:00 GMT
Pheochromocytoma is a neuroendocrine tumor of the adrenal glands. Pheochromocytoma patients display the signs and symptoms of those of sympathetic nervous system hyperactivity. Up to 36% of patients worldwide with pheochromocytoma develop metastatic disease and have a 5-year survival rate of approximately 50% after diagnosis. Patients with metastatic pheochromocytoma exhibit excessive levels of circulating catecholamines, which results in increased risk of strokes, cardiac arrhythmias, and hypertensive complications. Current treatments for malignant pheochromocytoma include targeted radiation using [¹³¹I]-metaiodobenzylguanidine ([¹³¹I]-MIBG), cytotoxic chemotherapy, octreotide, tumor hemoembolization, etc. The success of these treatments varies based on the sites and growth rate of metastatic lesions.

The present invention provides a method for treating a mammalian tumor with a histone deacetylase inhibitor (HDACi), and followed by administering [¹³¹I]-MIBG. Methods of diagnosis and imaging of mammalian tumors are also disclosed. These findings suggest that HDACi could enhance the therapeutic efficacy of [¹³¹I]-MIBG treatment in patients with malignant pheochromocytoma. CRADA Opportunity: The National Institute of Child Health and Human Development, Reproductive Biology and Adult Endocrinology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize [¹³¹I]-MIBG treatment of malignant/metastatic pheochromocytoma, paraganglioma, and neuroblastoma; also [^123/131I]-MIBG scintigraphy - in all situations histone deacetylase to be used before MIBG is used. Please contact Joseph Conrad, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information. Click here to view the NICHD collaborative opportunity announcement.

BODIPY®-FL Nilotinib (Tasigna®) for Use in Cancer Research

Mon, 01 Mar 2010 17:00:00 GMT
Investigators at the National Institutes of Health have produced a fluorescently labeled derivative of the clinically-approved, tyrosine kinase inhibitor (TKI) nilotinib (Tasigna®) for use in research. This was accomplished by conjugating the fluorescent dye BODIPY®-FL to nilotinib.

The TKI imatinib (Gleevec®) is the first targeted therapeutic developed and is used as first line treatment of Philadelphia chromosome-positive (Ph+) cancers like chronic myeloid leukemia (CML). Although imatinib is highly effective, after continued use the cancer cells frequently become resistant to the drug. Nilotinib is a second generation TKI developed to overcome imatinib resistance, but eventually it can also result in drug resistance.

The fluorescent nilotinib conjugate was developed to study the mechanism by which cancer cells become resistant to nilotinib and better understand its cytotoxic effects. CRADA Opportunity: The National Cancer Institute, Transport Biochemistry Section, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize bodipy conjugated tyrosine kinase inhibitors that are currently used in the clinic for the treatment of CML or gastric cancers. We are also interested in evaluating third generation tyrosine kinase inhibitor derivatives as modulators of ABC drug transporters to improve the efficiency of chemotherapy in animal (mouse) model system. In addition, we can identify possible pharmacokinetic interactions of the novel kinase inhibitors with ABC drug transporters. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Diagnostic Biomarker of Metastasis for Improved Clinical Management of Head and Neck Cancer

Mon, 01 Mar 2010 22:00:00 GMT
Squamous Cell Carcinoma of the Head and Neck (HNSCC) is associated with poor prognosis due to the advanced stage of disease (metastasis) typically found at the time of diagnosis. Investigators at the NIH have developed a sensitive method using a protein biomarker for detecting even just a few HNSCC tumor cells in lymph nodes with occult disease. Combination of this staging technique with intraoperative sentinel lymph node mapping would improve the management of HNSCC by identifying patients for which radical lymph node dissection is most appropriate, sparing those for which it is not, and informing decisions for adjuvant cancer therapy during a single surgery.

This technology arose from the discovery that the Desmoglein-3 (DSG3) protein which is highly expressed in tumors of squamous epithelial origin, like HNSCC, is also expressed in invaded lymph nodes but it is not found in normal lymph nodes. Therefore, DSG3 can serve as a biomarker for detecting metastastatic spread of squamous cell carcinoma tumors. This is achieved by performing protein detection immunoassays to samples (biopsy, aspirate, or isolated cells) of suspect lymph nodes. CRADA Opportunity: The NIDCR, OPCB, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of DSG3 as a biomarker for detecting metastastatic spread of squamous cell carcinoma tumors. Please contact David W. Bradley, Ph.D. at bradleyda@nidcr.nih.gov for more information.

Novel Kinase Inhibitors Targeting the PH Domain of AKT for Preventing and Treating Cancer

Tue, 02 Mar 2010 03:00:00 GMT
Activation of the PI3K/Akt signaling pathway has been implicated in the development of cancer. Akt, a kinase that is central to this pathway, is found at elevated levels in many tumors and is associated with a poor disease prognosis. Many research studies have validated Akt as a therapeutic target for the development of anti-cancer drugs. Most efforts of drug development targeting Akt have focused on inhibitors of the ATP-binding domain which tend to interfere with other physiologically important kinases. An alternative strategy that has been proposed to improve drug specificity is the targeting of the unique pleckstrin homology (PH) domain of Akt.

Investigators at the National Institutes of Health have screened a library of small chemical compounds with drug-like characteristics that likely bound to the PH domain and have identified several candidates previously unknown to interact with Akt. These compounds were tested and found to inhibit Akt activity specifically through the PH domain. Some of these compounds demonstrated broad cytotoxicity to a wide variety of tumor cells. These novel Akt-inhibiting compositions target the PH domain and help in the prevention and treatment of cancer. Since it has been shown that reducing the activity of the PI3K-Akt pathway sensitizes malignant cells to chemotherapy or radiotherapy, these novel Akt inhibitors have potential either as single anti-cancer agents or in combination with conventional cancer therapies.

One of the candidate compounds inhibited Colony Stimulating Factor-1 Receptor (CSF1R) from binding to ATP but had no activity for other kinases. CSF1R has been implicated in development of cancers like chronic myelomonocytic leukemia, but also in Alzheimer's disease so this specific compound may have use in treating other diseases in addition to cancer. CRADA Opportunity: The Center for Cancer Research, Medical Oncology Branch and Affiliates, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Patient-derived Gastrointestinal Stromal and Paraganglioma Tumor Samples Harboring Novel Stem Cell Factor FOXD3 Variants

Mon, 01 Mar 2010 08:00:00 GMT
The cancer market is forecast to reach $40 billion dollars by the year 2012. There is still a significant need to develop new therapies for treating sarcomas and malignant neoplasms.

Researchers at the National Institute of Child Health and Human Development (NICHD), NIH, have made available samples of patient-derived gastrointestinal tumors (GIST) and paraganglioma tumors that harbor genetic mutations that have an effect on early stage embrogenesis which plays a role in the fate of stem cells. GISTs are one of the most common sarcomas of the gastrointestinal tract with an estimated 5,000-10,000 new cases in the U.S. reported each year. GISTs affect mainly pediatric and young adult patients, and respond poorly to current therapies. Paragangliomas are rare neuroendocrine neoplasms that develop primarily in the abdomen.

The tumor samples made available herein contain deletions in the FOXD3 gene and display down-regulated FOXD3 protein expression. While the majority of GISTs result from activating mutations in the oncogene receptor tyrosine kinases c-KIT and PDGFRA, these tumor samples do not harbor mutations in c-KIT or PDGFRA ("non-KIT/ PDGFRA-GISTs") and respond poorly to receptor tyrosine kinase inhibitors. CRADA Opportunity: The National Institute of Child Health and Human Development Endocrinology & Genetics Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Joseph Conrad, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information.

Compounds that Interfere with the Androgen Receptor Complex: Use in Treating Prostate Cancer or Enlargements, Diabetes, and as Contraceptives

Mon, 01 Mar 2010 13:00:00 GMT
Investigators at the National Institutes of Health (NIH) have discovered compounds that have potential as novel anti-androgen therapeutics. The immunophilin protein FKBP52 is part of a protein complex that helps fold the androgen receptor (AR) protein, a target for treating prostate cancer, and enhances its activity. Disruption of the FKPB52-AR interaction greatly reduces the activity of the AR. With the goal of finding potential therapeutic compounds that inhibit the FKBP52-mediated activation of AR, several small molecules were tested and found to be antagonists of FKBP52 and to inhibit AR activity in prostate cells. These compounds can serve as therapeutics for the treatment of prostate cancer and benign prostate enlargement. Moreover, FKBP52 is also implicated in the regulation of other hormone receptors so these compounds could be used to treat other hormone-dependent diseases such as diabetes or even used as contraceptives.

One of the standard treatments for prostate cancer makes use of anti-androgens, like bicalutamide, which compete for binding with the natural male hormones to AR and inhibit their proliferative activity. The problem with available anti-androgen drugs is that prostate tumors eventually become drug resistant resulting in so-called androgen-resistant prostate cancer. One cause of this is an increase in the levels of AR produced by the prostate cancer cells. A solution to this problem may lie in disrupting the protein folding of AR by interfering with its interaction with FKBP52 using these compounds. CRADA Opportunity: The Center for Cancer Research, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antagonists of FKBP52-dependent remodeling of the androgen receptor. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Detection of Autoantibodies for the Diagnosis of Sjogren's Syndrome

Mon, 25 Jan 2010 18:00:00 GMT
This invention provides a method for diagnosing Sjogren's syndrome in a subject. In tests utilizing blood from human volunteers, this method demonstrated dramatically higher accuracy (76%) in positively diagnosing Sjogren's syndrome than a standard, currently available immunoassay (46%).

Briefly, this invention employs a panel of mammalian-derived proteins and protein fragments that are often antigentic in individuals with Sjogren's syndrome in concert with a luciferase immunoprecipitation system. In contrast, most currently available immunoassays for diagnosis of rheumatological diseases include either antigens from recombinant bacterial expression systems or single antigens from bovine sources. These immunoassays are likely to fail to present the sufficient variety of specific human epitopes that are necessary for high accuracy diagnoses of Sjogren's syndrome. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Laboratory of Sensory Biology, Neurobiology and Pain Therapeutics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

Novel Analogues of the Natural Product Schweinfurthin with Specificity for Tumors and Other Disease Manifestations Associated with Neurofibromatosis Type 1

Mon, 25 Jan 2010 23:00:00 GMT
The global anti-cancer market is forecast to reach $40 billion by 2012. There remains a significant unmet need for therapies to treat neurofibromatosis type 1 ("NF1"), a common genetic disease that afflicts 1 in 3500 people, and malignant tumors carrying NF1 mutations, including tumors of the central and peripheral nervous systems.

Researchers at the National Cancer Institute ("NCI")-Frederick investigating genetic influences on cancer susceptibility of the nervous system have synthesized novel analogues of Schweinfurthin, a natural compound first isolated from the tropical African plant Macaranga schweinfurthii, to which glioma and leukemia cell lines show significant sensitivity. The Schweinfurthin analogues also have inhibitory activity against mouse and human NF1 cancer cell lines. The analogues have a novel mode of action that appears to involve regulation of cytoskeletal reorganization.

These inhibitors are likely to be accepted in the marketplace because their potent, selective activity and unique specificity in mode of action gives them a distinct advantage over the mechanisms of other existing therapies. CRADA Opportunity: The Genetic Modifiers of Tumorigenesis Section at the National Cancer Institute-Frederick is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Schweinfurthins for the treatment of Neurofibromatosis type 1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Mouse Macula Densa Cell Line

Tue, 26 Jan 2010 04:00:00 GMT
This technology provides a clonally derived macula densa cell line (MMDD1 cells) that closely mimics the known molecular expression pattern of native macula densa (MD) cells. MMDD1 cells are developed from SV-40 transgenic mice using fluorescence-activated cell sorting of renal tubular cells labeled with segment-specific fluorescent lectins. The MMDD1 cells of this technology express COX-2, bNOS, NKCC2, and ROMK, but not Tamm-Horsfall protein, and show rapid ⁸⁶Rb⁺ uptake that is inhibited by a reduction in NaCl concentration and by bumetanide or furosemide. These MMDD1 cells provide a useful in vitro model for the study of Macula Densa function. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases Kidney Disease Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the clonally derived macula densa cell line (MMDD1 cells). Please contact Cindy Fuchs at 301-451-3636 for more information.

Method for the Treatment of HIV/AIDS Infection Using Acyclovir in Identified Subjects

Mon, 25 Jan 2010 09:00:00 GMT
The invention provides the novel method to treat HIV infections with acyclovir which can be converting to acyclovir triphosphate inside infected cells. Acyclovir or acyclovir-related drugs were previously approved for control of herpesvirus replication with 20 years of records of safe application. The subject invention demonstrates that acyclovir triphosphate can inhibit HIV-1 reverse transcriptase as a potent suppressor of HIV-1 replication in human lymphoid tissues. In addition, the subject invention may be attractive to potential licensees, as there is little to not FDA hurdle to overcome in the development of the new formulations to use in this manner. Thus, the low cost and proven safety of acyclovir may lead to a new medicine for treating HIV-1 infections and a prophylactic agent for preventing HIV infections. CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Program in Physical Biology, Section on Intracellular Interactions, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Joseph Conrad, Ph.D., J.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information.

Signal-to-Noise Enhancement in Imaging Applications Using a Time-Series of Images

Mon, 25 Jan 2010 14:00:00 GMT
The invention offered for licensing relates to the field of imaging and specifically to the field of medical imaging. The apparatus and method of the invention provide for noise reduction in imaging applications that use a time-series of images. In one embodiment of the invention, a time-series of images is acquired using a same imaging protocol of the same subject area, but the images are spaced in time by one or more time intervals (e.g. 1, 2, 3 …seconds apart). A sub-region is projected across all of the images to perform a localized analysis (corresponding X-Y pixels or X-Y-Z voxels are analyzed across all images) that identifies temporal components within each sub-region. Subsequently, within the sub-regions, only those temporal components are selected whose amplitude is above a predetermined amplitude threshold. The images are then reconstructed using the sub-regions with reduced components. A maximal-intensity-projection (MIP) is applied in the temporal domain (tMIP) in order to obtain a single image with reduced noise (this can be done either at the sub-region level or at the reconstructed image level). The technology can be applied to a broad spectrum of medical imaging technologies such as MRI, X-Ray, CT and others. CRADA Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to implement the technology described above on specific commercial platforms. Please contact Denise Crooks, Ph.D. at 301-435-0103 or via e-mail at crooksd@nhlbi.nih.gov for more information.

Diagnostic Tool for Diagnosing Benign Versus Malignant Thyroid Lesions

Fri, 22 Jan 2010 19:00:00 GMT
This technology describes a 72 gene model that has been developed for diagnosing less common forms of thyroid cancer like follicular carcinoma and others. The technology detects thyroid cancer using fine needle aspiration (FNA) biopsy and the analysis of differentially expressed thyroid (DET) genes and their encoded proteins. These results provide a molecular classification system for thyroid tumors and this in turn provides a more accurate diagnostic tool for the clinician managing patients with suspicious thyroid lesions. It is related to earlier technology out of the laboratory of Dr. Libutti, US Application No. 11/547,995 entitled "Diagnostic Tool for Diagnosing Benign vs. Malignant Thyroid Lesions" (HHS Reference No. E-124-2004). This latter invention was drawn to a 6 and 10 gene model that distinguishes benign vs. malignant papillary thyroid lesions. CRADA Opportunity: The Center for Cancer Research, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Diagnostic Tool for Diagnosing Benign Versus Malignant Thyroid Lesions. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Mutations of the ERBB4 Gene in Melanoma

Sat, 23 Jan 2010 00:00:00 GMT
Cutaneous malignant melanoma is the most common fatal skin cancer, and the incidence of this disease increases each year. The average survival time for patients diagnosed with malignant melanoma is less than ten months. Consequently, it is important to identify and understand genetic alterations leading to malignant melanoma so that new treatments strategies can be developed.

Protein tyrosine kinases (PTKs) have been associated with a wide variety of cancers, including melanoma. Using high-throughput gene sequencing, the NIH inventors have analyzed PTKs in melanoma and have identified several novel somatic alterations, including alterations in ERBB4. This invention provides methods of identifying specific inhibitors to ERBB4 that could be used to treat patients with ERBB4 mutations. Given the recent success of small molecule protein kinase inhibitors and specifically inhibitors to EGFR, this invention could be used further the development of specific inhibitors to ERBB4 and improve existing melanoma treatments for patients with these mutations. CRADA Opportunity: The Cancer Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate and/or commercialize an ERBB4-based diagnostic, prognostic and/or theranostic test as well as identify and/or evaluate ERBB4 inhibitor compounds for testing as possible candidate malignant melanoma therapeutic drugs. Please contact Claire Driscoll at cdriscol@mail.nih.gov or Dr. Yardena Samuels at samuelsy@mail.nih.gov for more information.

Preventing Oral Mucositis with Hybrid Adenoretroviral Vectors

Fri, 22 Jan 2010 05:00:00 GMT
Researchers at the National Institutes of Health have recently developed a novel method utilizing adenoretroviral vectors to safely and swiftly prevent oral mucositis induced by radiotherapy. This clever new method developed by National Institute of Dental and Craniofacial Research (NIDCR) researchers combines the advantages of adenoviral and retroviral vectors to efficiently shuttle into salivary glands a non-integrating vector that can produce a therapeutic protein for intermediate to long-term treatment. This approach is anticipated to result in fewer side-effects than current therapies.

The market for the treatment of mucositis, the painful inflammation and ulceration of the mucous membranes lining the digestive tract, is estimated to be in excess of $5 billion world-wide. Up to 80% of all patients receiving radiotherapy and approximately 40% of all chemotherapy patients develop oral mucositis, and almost all patients receiving radiotherapy for head and neck cancer and those undergoing stem cell transplantation develop mucositis. CRADA Opportunity: The National Institute of Dental and Craniofacial Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

Non-Contact Total Emission Detection Methods for Multiphoton Microscopy: Improved Image Fidelity and Biological Sample Analysis

Mon, 28 Dec 2009 10:00:00 GMT
The technology offered for licensing and for further development is in the field of multiphoton microscopy (MPM). More specifically, the invention describes and claims optical designs that can enhance and extend the capabilities of MPM in spectral imaging of biological samples. The unique design of the light collection and the detection optics maximizes the collection of emitted light, thus increasing the signal and hence the signal-to-noise ratio (SNR). Improvement in image fidelity will result in improved analysis of biological samples and thus will favorably impact medical research and possibly clinical diagnosis. The present technology is a further improvement on the TED (Total Emission Detection) technology, first disclosed by Dr. Robert Balaban et al. at the NIH in 2006 and claimed in US patent application 11/979,600, now allowed (Patent Publication US-2008-0063345 A1, March 13, 2008). The earlier NIH TED technology proposed an optical design based on enveloping the entirety of a small sample in a parabolic mirror/condenser combination so light emanated by a sample in all directions is redirected to the detector. The present technology further expands the capabilities of TED as its unique design employing parabolic, toric and conic mirrors ensures maximum light collection from large samples in cases where there is only access to one side of the tissues (e.g., in vivo or ex vivo). This is accomplished by the redirection of all attainable light (i.e., light escaping the tissue or a whole animal in the epi and sideway directions) to the detector. CRADA Opportunity: The NHLBI Laboratory of Molecular Biophysics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize an enhanced method of multiphoton microscopy that is suitable for the spectral imaging of biological samples. Please contact Brian W. Bailey, Ph.D. at bbailey@mail.nih.gov for more information.

Fourier X-ray Scattering and Phase-Contrast Imaging: Enhanced Contrast and Sensitivity of X-ray Images

Mon, 28 Dec 2009 15:00:00 GMT
The invention offered for licensing is broadly applicable to medical diagnostic imaging, biological imaging, industrial non-destructive testing, security screening, and other routine x-ray inspections. The invention provides a method and apparatus that can significantly improve and enhance the contrast and sensitivity of x-ray images. More specifically, the method described in the invention provides a technique to obtain in a single shot x-ray diffraction, differential phase-contrast, as well as the conventional absorption images. X-ray diffraction reveals information about microscopic structures in the imaged object from nanometer to micrometer scales which enables detection of specific materials and disease pathologies that are invisible in conventional x-ray images. The main advantage of the invention over prior art is the single-shot capability without the need to scan an analyzer crystal or grating, and without the need for any hardware beyond standard radiography equipment. It also offers flexibility in hardware configuration to target specific materials by their diffraction signature. For this reason the invention is highly adaptable and well suited for day-to-day applications of x-ray radiography and computed tomography.

In one of the embodiments of the invention for example, a scattering imaging method uses a transmission grid to modulate the intensity of a beam of an x-ray radiation source. A detector captures a raw image from the modulated intensity pattern. A diffraction image can be automatically generated from the detected modulated intensity pattern.

In yet another embodiment, both a diffraction image and a differential phase-contrast image are obtained in a single exposure. Advantageously, commercially available x-ray grids and radiography machines can be used for this method, and exact positioning of the grid is unnecessary, as the method works for any non-zero distance between the grid and the detector. Thus, the speed and ease of implementation makes it suitable for both planar radiography and 3D computed tomography. In addition to its medical diagnostics significance, the invention can be utilized in other, non-medical applications such as non-destructive inspections and security screening. CRADA Opportunity: The National Heart, Lung, and Blood Institute, Laboratory of Cardiac Energetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize single-shot x-ray diffraction and phase-contrast imaging. Please contact Denise Crooks at 301-402-5579 or crooksd@nhlbi.nih.gov for more information.

Method of Preventing and Treating Metastatic Disease

Mon, 28 Dec 2009 20:00:00 GMT
Cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy appears to arise from tumor cells that disseminated early in the course of disease but did not develop into clinically apparent lesions. These long-term surviving, disseminated tumor cells maintain a state of dormancy, but may be triggered to proliferate through largely unknown factors. Inventors at the National Institutes of Health have discovered agents that prevent or treat recurrent metastatic cancer by inhibiting type I collagen production and downstream signaling through beta 1 integrin activation. Blocking activation of beta-1 integrin signaling using pharmacological approaches or using RNA interference was found to prevent reorganization of the cytoskeleton that is associated with proliferation of the dormant tumor cells. The technology provides compositions and methods for modulating the switch from tumor cell dormancy to proliferation clinical metastatic disease in a patient by administering beta-1 integrin signaling inhibitors. CRADA Opportunity: The Center for Cancer Research, Laboratory of Cancer Biology and Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Optimizing Chemotherapeutic Performance: Three Newly-Identified Classes of Tyrosyl-DNA Phosphodiesterase (Tdp1) Inhibitors

Tue, 29 Dec 2009 01:00:00 GMT
During replication, DNA is structurally modified and cleaved by a host of enzymes, including topoisomerases. Some chemotherapeutic agents generate their anti-cancer activity by inducing DNA damage in rapidly replicating tumor cells, resulting in cell death. Topoisomerase I (top1) inhibitors, such as camptothecins, are common chemotherapeutics that prevent the religation of DNA after cleavage during replication.

Tyrosyl-DNA phosphodiesterase (Tdp1) counteracts the action of these chemotherapeutic agents and can reduce their effectiveness in eliminating tumor cells. Tdp1 is an enzyme that repairs DNA lesions and chemotherapeutic-mediated DNA damage, such as the DNA breaks induced by top1 inhibitors. Therefore, Tdp1 is a rational anticancer target whose inhibition should enhance the activity of common cancer chemotherapeutics by permitting greater DNA damage in tumor cells.

Scientists at the National Institutes of Health (NIH) have discovered three classes of compounds that specifically inhibit Tdp1, including cephalosporin derivatives like beta-lactam antibiotics, ellagic acid derivatives such as polyphenol antioxidants, and verteporfin derivatives including protoporphyrins. The compounds were identified as specific Tdp1 inhibitors via a high-throughput screening assay (AlphaScreen^TM) of the NIH Roadmap Molecular Libraries Small Molecule Repository (MLSMR). One current goal of the scientists is to identify the compounds with the greatest Tdp1specificity and highest inhibitory activity against cancer cell proliferation. Some of the compounds identified are widely used to treat a variety of other diseases, including bacterial infections (beta-lactam antibiotics) and neurodegenerative and cardiovascular disorders (polyphenol antioxidants).

Now, through studies at the NIH, these compounds identified as Tdp1 inhibitors could be utilized to potentiate the pharmacological action of top1 inhibitors in the treatment of cancer with combination drug therapies. Top1 inhibitor/Tdp1 inhibitor combination chemotherapies are anticipated to be more selective against tumor tissues than top1 inhibitors alone. In addition, since Tdp1 is involved in repairing DNA damage caused by oxygen radicals and tumors are known to contain excess free radicals, Tdp1 inhibitors may also prove useful as anticancer agents independent of their use in conjunction with top1 inhibitors. CRADA Opportunity: The National Cancer Institute, Laboratory of Molecular Pharmacology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize topic of invention or related laboratory interests. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

A Device for Sterile Removal of a Biological Sample from a Cryopreserved Bag

Mon, 28 Dec 2009 06:00:00 GMT
Cryopreservation through freezing in liquid nitrogen allows the storage of biological materials for extended periods while maintaining their activity and viability. It is commonly used in the clinic to store blood cells, semen, and umbilical cord blood (UCB) for future use. These materials are typically only obtainable in limited quantities and may be of great therapeutic value, as is the case of hematopoietic stem cells from UCB which can be used to treat and cure a number of different life-threatening illnesses. It is common practice to cryopreserve viably in bags a variety of different cells obtained from the blood . Currently, even if only a small portion of the cryopreserved sample is needed the whole bag must be thawed, wasting much of the sample since it cannot be effectively refrozen. There is a need for a method of retrieving a small sample from a frozen sample of cells in a bag while preserving the cryopreserved state and integrity of the rest of the cellular material.

Researchers at the National Heart, Lung, and Blood Institute in collaboration with the American Fluoroseal Corporation (AFC) have invented an apparatus that separates a small portion of a cryopreserved biological material stored in a collection bag while maintaining the cryopreserved integrity, sterility, and viability of the original cryopreserved material. This device could be used to retrieve small aliquots samples of various cryopreserved cellular products and biological materials such as UCB, blood mononuclear cells, stem cells, semen, and plasma while maintaining the viability and sterility of both the retrieved sample and the original cryopreserved material. CRADA Opportunity: The National Heart, Lung, and Blood Institute, Hematology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the Device for Sterile Removal of a Biological Sample from a Cryopreserved Bag. Please contact Cecilia Pazman, Ph.D., 301-402-5579; pazmance@mail.nih.gov for more information.

Synergy of ABT-737 with an Immunotoxin to Kill Cancer Cells

Mon, 28 Dec 2009 11:00:00 GMT
Programmed cell death (i.e., apoptosis) represents an attractive approach for treating cancer. However, anti-apoptotic proteins that are frequently active in cancer cells can allow the cells to survive induction of apoptosis. While inhibiting anti-apoptotic proteins has shown promise in combination with apoptosis-inducing treatments, current inhibitors only show incomplete effectiveness in promoting the induction of apoptosis.

ABT-737 is one such inhibitor; it can only inhibit the function of three of the four major anti-apoptosis proteins. The fourth member, known as a MCL1, is a short-lived protein that can still prevent apoptosis in the presence of ABT-737. Importantly, because MCL1 is a short-lived protein, it requires protein synthesis to maintain levels that are sufficient to continue blocking apoptosis.

This technology uses a combination approach in the treatment of cancer. The inventors considered that combining ABT-737 with a protein synthesis inhibitor might completely inhibit anti-apoptotic proteins, leading to efficient induction of apoptosis. Specifically, NIH inventors found that combining ABT-737 and immunotoxins did result in enhanced killing of cancer cells. Because immunotoxins function by inhibiting protein synthesis, the two agents in combination are able to inhibit all of the anti-apoptotic proteins simultaneously. Furthermore, immunotoxins can be specifically targeted to cancers cells, thereby increasing their effectiveness over a non-specific protein synthesis inhibitor. The results suggest that the combination could represent an effective approach to enhancing the induction of apoptosis as an anti-cancer therapy. CRADA Opportunity: The Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Vaccines Against Malarial Diseases

Wed, 23 Dec 2009 16:00:00 GMT
The invention offered for licensing is in the field of use of vaccines for malaria. The invention provides gene sequences encoding an erythrocyte binding protein of a malaria pathogen for the expression of the erythrocyte binding protein. The codon composition of the synthetic gene sequences approximates the mammalian codon composition. The synthetic gene sequences are useful for incorporation into DNA vaccine vectors, for the incorporation into various expression vectors for production of malaria proteins, or both. The synthetic genes may be modified to avoid post-translational modification of the encoded protein in other hosts. Administration of the synthetic gene sequences, or the encoded protein, as an immunization agent is useful for induction of immunity against malaria, treatment of malaria, or both. The approach presented in this invention, i.e. vaccine that may block the binding of the malaria parasite and subsequent erythrocyte invasion, may work independently or in combination with other vaccines which are based on different mechanisms. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the erythrocyte binding protein as a malaria vaccine. Please contact Dana Hsu at 301-496-2644 for more information.

Device and Method for Direct Measurement of Isotopes of Expired Gases: Application in Research of Metabolism and Metabolic Disorders, and in Medical Screening and Diagnostics

Wed, 23 Dec 2009 21:00:00 GMT
The technology offered for licensing and for further development concerns a novel device for intervallic collection of expired gas from subjects and subsequent measurement of the isotopic content of such expired gases. The device is specifically designed for medical research and clinical applications, and in particular in the area of metabolic disorders. The device may facilitate the development and testing of new therapies for such disorders and may be used for medical screening and diagnostics of metabolic diseases. The unique design of the device includes a constant volume respiratory chamber equipped with a series of valves and stopcocks to allow precise and repetitive removal of expired gases, and addition of air or other gas to maintain the chamber at a constant volume. Also included is a vacuum tube adapter linked to a port on a three-way stopcock to allow facile transfer of the chamber gases to vacuum tubes for subsequent chemical analyses. The device also includes gas sensors operably linked to detectors and inserted to the chamber through airtight ports; this allows the operator to independently and directly measure the carbon dioxide production rate and oxygen consumption of the test subject while the expired gases are removed for study.

The experimental subject (e.g. mammal) is first contacted with a substrate (e.g. amino acid, fatty acid, organic acid) containing an isotope (e.g. ¹³C) and placed in the chamber. The unique design allows easy gas removal and addition while maintaining a constant chamber volume. Precisely measured air samples are collected from the chamber by the syringe and subsequently transferred to a self-sealing vacuum tube which is then removed for analysis. Subsequent sampling is accomplished in the exact same manner, after an equivalent volume of ambient air, or other gas such as pure oxygen, is reinjected in the chamber to maintain pressure and volume. Air samples from the chamber are collected periodically and the content of the isotope (¹³C) accumulated in the chamber gas due to metabolism and the formation of ¹³CO₂ is measured (e.g. via Isotope Ratio Mass Spectroscopy (IRMS)) from the collected samples. The rate of the metabolite's development (i.e. ¹³CO₂) can thus be determined and can thus provide information on the metabolic status of the subject, such as the rate and extent of oxidation of the administered isotope. Furthermore, results of such analysis can provide fundamental information on the ability of the subject to metabolize a compound, quantitate the effectiveness of an experimental therapy (i.e. enzyme replacement, gene therapy, hormone administration, etc.) and thus facilitate progress in the development of interventional therapies. CRADA Opportunity: The Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute (NHGRI), is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology or related laboratory interests. Please contact Claire T. Driscoll at cdriscol@mail.nih.gov for more information.

Small-Molecule Inhibitors of Angiogenesis

Thu, 03 Dec 2009 02:00:00 GMT
Angiogenesis, the growth of new blood vessels from existing vessels, is a normal and vital process in growth and development. Deregulation of angiogenesis plays a role in many human diseases, including cancer, age-related macular degeneration, diabetic retinopathy, and endometriosis.

NCI investigators have used a cell-based high-throughput screening method to identify a set of anti-angiogenic small molecules. These compounds are highly active, inhibiting both endothelial cell growth and tube formation, and are not cytotoxic. Structure-activity relationship analysis has revealed that these compounds are unrelated to known anti-angiogenic compounds, and hence may operate through a novel mechanism of action. Thus, these compounds would be promising candidates for the development of new anti-angiogenesis therapeutics. CRADA Opportunity: The National Cancer Institute Angiogenesis Core Facility is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a new set of non-cytotoxic antiangiogenic small molecules. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Antibody Composition and Methods for the Prevention and Treatment of Lupus Nephritis

Mon, 30 Nov 2009 07:00:00 GMT
This technology identifies an antibody that induces a protective effect in vivo in a mouse model of lupus nephritis. Lupus is a chronic autoimmune disease that can damage various parts of the body, especially the kidneys. The lupus nephritis-model mice that were treated with this antibody experienced a dramatic increase in survival, demonstrated a reduced immune complex formation deposition in the kidneys, and displayed low levels of proteinuria as compared with untreated mice. The antibody is an autospecific anti-dsDNA IgM.

In addition, this invention may be used as a component of a predictive diagnostic kit. As lupus-related kidney disease may be asymptomatic, significant kidney damage may occur before lupus is diagnosed (lupus.org). The inventors are currently investigating whether the ratio of protective antibodies to nonprotective or pathogenic antibodies in lupus nephritis models is predictive of disease. Currently available diagnostic methods (proteinuria, creatine clearance, or kidney biopsy) are not predictive and test only for existing kidney impairment or damage. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology or related laboratory research interests. Please contact Dr. Elizabeth Denholm at denholme@niehs.nih.gov or 919-541-0981 for more information.

RORgamma (RORC) Deficient Mice Which Are Useful for the Study of Lymph Node Organogenesis and Immune Responses

Mon, 23 Nov 2009 12:00:00 GMT
The retinoid-related orphan receptor gamma (RORgamma) is a member of the nuclear receptor superfamily. NIH investigators used homologous recombination in embryonic stem cells to generate mice in which the RORgamma gene was disrupted. RORgamma deficient mice lack peripheral and mesenteric lymph nodes and Peyer's patches indicating that ROR expression is indispensable for lymph node organogenesis. In addition, RORgamma is required for the generation of Th17 cells which play a critical role in autoimmune disease.

The RORgamma deficient mice are useful to identify the physiological functions of the RORgamma. RORgamma deficient mice also provide an excellent tool to study the role of RORgamma in immune responses and autoimmune disease, the study of the role of Th17 and interleukin 17 in these processes, and the analysis. CRADA Opportunity: The NIEHS is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the ROR gamma mice or related laboratory research interests. Please contact Dr. Elizabeth Denholm at denholme@niehs.nih.gov or 919-541-0981 for more information.

Potent and Selective Inhibitors of Human Lipoxygenase for Prostate Cancer Therapy

Tue, 17 Nov 2009 17:00:00 GMT
With more than $2 billion in revenues in the US in 2007, the market for diagnostic and therapeutic products for prostate cancer is substantial. More than 2,000,000 American men currently live with prostate cancer and more than 200,000 new cases are diagnosed each year.

Researchers led by Dr. David Maloney at the National Human Genome Research Institute (NHGRI) have discovered several novel compounds that selectively and potently inhibit lipoxygenase (LOX), an enzyme that metabolizes polyunsaturated fatty acids which has been implicated in the pathogenesis of prostate cancers. These novel compounds are small molecules, and as such have an advantage over antibody-based technologies in this market. As prostate cancer is the most commonly diagnosed malignancy among men in the USA and Europe, the significant need for new therapies suggests that these novel LOX inhibitor compounds have a strong potential of reaching the marketplace. CRADA Opportunity: The NIH Chemical Genomics Center, NCATS, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Lili M. Portilla, MPA at 301-217-2589 or Lilip@nih.gov for more information.

Optimized Expression of IL-12 Cytokine Family

Tue, 17 Nov 2009 22:00:00 GMT
The IL-12 family of cytokines (IL-12, IL-23, and IL-27) has an important role in inflammation and autoimmune diseases. IL-12 is produced by macrophages and dendritic cells in response to certain bacterial and parasitic infections and is a powerful inducer of IFN-gamma production. IL-23 is proposed to stimulate a subset of T cells to produce IL-17, which in turn induce the production of proinflammatory cytokines that lead to a protective response during infection. IL-27 appears to have duel functions as an initiator of TH1-type (cellular immunity) immune responses and as an attenuator of immune/inflammatory responses.

The present inventions provide methods for improved expression of multimeric proteins by engineering different ratios of the subunit expression units in a cell or upon expression from a multi-promoter plasmid having different strength promoters. The inventors have improved the levels and efficiency of expression of the IL-12 family of cytokines, which includes IL-12, IL-23, and IL-27, by adjusting the transcription and translation of the alpha and beta subunits that comprise the heterodimeric proteins. Optimal ratios of expression for the two (2) subunits were determined for IL-12, IL-23, and IL-27. CRADA Opportunity: The Center for Cancer Research, Human Retrovirus Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize delivery of cytokines of the IL-12 family in cancer and other indications. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Immunotoxin Useful for Treatment of AIDS

Thu, 05 Nov 2009 03:00:00 GMT
Human Immunodeficiency Virus (HIV) attacks and destroys T cells, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) in patients. Although significant progress has been made treating patients with AIDS, an effective cure has yet to be identified. For example, highly active antiretroviral therapy (HAART) has shown dramatic reduction of viral replication while allowing recovery of the immune system in HIV patients. However, HAART does not directly kill HIV-infected T cells, allowing the virus to persist in the body and resume replication and infection of T cells after HAART is stopped. This ultimately results in a return to pre-treatment levels of viral replication and the persistence of the disease in patients.

The current technology concerns an invention that can be used to address this limitation of HAART. An immunotoxin has been created that targets a toxin (PE38) to the HIV-specific Envelope glycoprotein (gp120) that is displayed on the surface of T cells that have been infected with the HIV virus. The immunotoxin kills the HIV-infected T cells and other infected cell types that serve as a viral reservoirs during HAART, thereby reducing the ability of the virus to replicate and infect other cells after HAART is stopped. Recent data shows that the immunotoxin blocks the spread of HIV-1 in vitro and does not induce hepatotoxicity in rhesus monkeys, suggesting the procedure could be effective in human patients. By combining the immunotoxin with a treatment regimen such as HAART, it may be possible to significantly improve treatment of HIV infection. CRADA Opportunity: The Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

A Phantom for Diffusion MRI: A Method of Enhancing Performance and Reliability

Wed, 04 Nov 2009 08:00:00 GMT
The technology offered for licensing is in the field of Diffusion Magnetic Resonance Imaging (Diffusion MRI). Specifically, a novel imaging phantom is described and claimed. Such a phantom is specifically optimized for Diffusion MRI and is expected to enhance the performance and reliability of this now widespread imaging technology.

The phantom provided in this invention comprises a stable aqueous solution with a concentration of at least 30%, by weight, of a mixture of a high molecular-weight polymer or copolymer and a low molecular-weight polymer or copolymer, the aqueous solution having a resulting water diffusivity from about 2x10^-4 mm²/s to about 3x10^-3 mm²/s. Polyvinyl Pyrrolidone (PVP) is the polymer of choice used in this invention. The phantoms of this invention are uniquely stable, non-toxic, and transportable, and have shown to maintain constant water diffusivity after two years. CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development's Section on Tissue Biophysics & Biomimetics (STBB) is seeking statements of capability or interest from outside parties who are interested in entering into a Collaborative Research and Development Agreement (CRADA) to develop and commercialize the Diffusion MRI Phantom described above. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information.

Treating Cancer with Anti-Angiogenic Chimeric Antigen Receptors

Wed, 04 Nov 2009 13:00:00 GMT
Metastasis, the growth and spread of cancer from a localized tumor to other sites in the body, is promoted by the formation of new blood vessels through angiogenesis to "feed" the tumor. There is an urgent need to develop new therapeutic strategies that combine fewer side-effects and more specific anti-tumor activity in order to block cancer metastasis in patients. Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual's innate and adaptive immune system to fight against specific diseases, including the spread of cancer.

Chimeric antigen receptors (CARs) are hybrid proteins consisting of the portion of an antibody that recognizes a tumor-associated antigen (TAA) fused to protein domains that signal to activate the CAR-expressing cell. Human cells that express CARs, most notably T cells, can recognize specific tumor antigens in an MHC-unrestricted manner with high reactivity. CARs are able to mediate an immune response that promotes robust tumor killing in targeted cells.

Scientists at the National Institutes of Health (NIH) have developed CARs with high affinity for the vascular endothelial growth factor receptor 2 (VEGFR2) (also known as kinase domain region (KDR) in humans and fetal liver kinase-1 (Flk-1) in mice) to utilize as an antiangiogenic tumor therapy. VEGFR2 is expressed on non-cancerous vascular endothelia cells, but is overexpressed on tumor endothelial cells in a variety of cancers, especially solid tumors. VEGFR2 overexpression promotes tumor vasculature, growth, and metastasis. The VEGFR2-specific CARs feature the antigen binding domain of the KDR-1121 or DC101 antibody, which recognize portions of the human and mouse VEGFR2, respectively. This antibody component is fused to the transmembrane and intracellular signaling domains of a T cell receptor (TCR). These CARs combine high affinity recognition of VEGFR2 provided by the antibody portion with the target cell killing activity of a cell expressing an activated TCR. Infusion of these VEGFR2-specific CARs into patients could prove to be a powerful new immunotherapeutic tool for blocking angiogenic cancer metastasis by killing VEGFR2+ tumor cells. CRADA Opportunity: The Center for Cancer Research, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Simpler is Better: The Production of Young Cell Cultures from Tumor Infiltrating Lymphocytes (TIL) Yields More Effective Adoptive Cell Transfer (ACT) Immunotherapies

Wed, 04 Nov 2009 18:00:00 GMT
Available for licensing is an improved method of adoptive cell transfer (ACT) immunotherapy that can be utilized to treat a variety of infectious diseases and cancers, most notably melanoma.

At its foundation, ACT involves isolating lymphocytes with high affinity for a particular antigen, expanding those cells in vitro to produce a greater quantity of reactive cells, and infusing the product cells into patients to attack cells expressing the antigen, such as tumor cells, bacterial cells, or viral particles. Previously utilized ACT procedures have been plagued by technical, regulatory, and logistical problems that have prevented consistently successful clinical outcomes. Through years of research, scientists at the National Institutes of Health (NIH) have made great strides in developing ACT into a viable approach to treat cancer patients. Of note, the ACT protocols developed by NIH scientists have successfully treated patients with refractory metastatic melanoma who started with very few effective treatment options. These NIH scientists have found that isolating cells from the tumor infiltrating lymphocytes (TIL) of a patient tumor sample provides a suitable initial lymphocyte culture for further in vitro manipulations. They have also discovered that taking the isolated cells through one cycle of rapid expansion (including exposure to IL-2), rather than multiple cycles, yields lymphocyte cultures with higher affinity and longer persistence in patients. Also, they have found that administering nonmyeloablative lymphodepleting chemotherapy prior to the reinfusion of lymphocytes creates a more favorable environment within patients for the transferred cells to execute target cell killing. These scientists envision that, for an ACT immunotherapy to gain regulatory approval and successfully treat a wide array of patients, it will need to be rapid, reliable, and technically simple. One of the most critical factors to this approach is the generation of effective lymphocyte cultures that will rapidly and repeatedly attack the target cells when infused into patients.

Scientists at the NIH have developed a method of generating CD8+ selected "young" lymphocyte cultures for infusion into cancer patients. Lymphocytes that spend fewer days in vitro between their initial isolation from TIL and their ultimate reinfusion into patients compared to lymphocytes cultured by previous ACT protocols are considered young lymphocyte cultures. Young lymphocytes, typically 19-35 days old when reinfused into patients, exhibit improved proliferation, survival, and enhanced anti-tumor activity within patients to yield greater tumor regression compared to older lymphocytes, typically 44+ days old. Furthermore, the generation of young lymphocyte cultures is more rapid, reliable, and technically easier than previous ACT culturing methods. Young lymphocytes are isolated from TIL, directed against a single isolated tumor cell suspension, enriched for CD8 expression, and rapidly expanded once using autologous feeder cells without testing the culture for antigen specificity.

This approach to ACT offers a potentially significant improvement and a valuable new immunotherapeutic tool for attacking tumors. For diseases, such as metastatic melanoma, where patients may only have weeks or months of life expectancy, this technology, which provides for improved cell cultures prepared in less time, can make a difference between life and death. In addition, this method might be applicable in treating other diseases such as AIDS, immunodeficiency, or other autoimmunity for which immune effector cells can impact the clinical outcome. CRADA Opportunity: The Center for Cancer Research, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cell and gene therapy technologies, and personalized medicines. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Viral Inactivation Using Crosslinkers and Detergents

Wed, 04 Nov 2009 23:00:00 GMT
The subject technology is a method of inactivating enveloped viruses by hydrophobic photoactivatable chemical crossing-linking compounds and detergent treatment. The inactivated viruses may be used as vaccines against the diseases caused by those viruses or as reagents in experimental procedures that require inactivated viral particles. The compounds diffuse into the lipid bilayer of biological membranes and upon UV irradiation will bind to proteins and lipids in this domain, thereby inactivating fusion of enveloped viruses with their corresponding target cells. Furthermore, the selective binding of these chemical crosslinking agents to protein domains in the lipid bilayer may preserve the structural integrity and therefore immunogenicity of proteins on the exterior of the inactivated virus. The additional detergent step effectively eliminates the infectivity of any residual viral particles that are not adequately crosslinked. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of hydrophobic crosslinkers for their use in vaccine development. Interested collaborators are also invited to provide statements for proposed in vitro or in vivo studies using various enveloped viruses. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Live-Attenuated Tularemia Vaccine

Fri, 30 Oct 2009 03:00:00 GMT
The invention provides compositions and methods of use for a modified strain of Francisella tularensis, the causative agent of tularemia, a category A biodefense agent (NIAID classification). Currently, no vaccines are available, and the only approved therapeutics for tularemia are antibiotics that are only effective if delivered early in the infection. The subject invention defines and characterizes mutations in Francisella tularensis that result in attenuated bacteria capable of inducing strong protective immune responses. Thus, these stable mutant strains could be used as efficient live vaccines against tularemia. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize live vaccine strains of Francisella tularensis with defined mutations. Please contact Rosemary Walsh at 301-496-2644 for more information.

A Novel Multimeric CD4 Fusion Protein for Treating HIV Infection

Thu, 29 Oct 2009 07:00:00 GMT
This invention could potentially provide an alternative to antiretroviral therapy (ART), especially in cases where productively-infected cells persist with ART. This multimeric CD4 fusion protein acts as a decoy to inhibit human immunodeficiency virus (HIV-1) entry into host cells. More specifically, this multimeric CD4 inhibits the interaction between HIV-1 gp120 and CD4 present on the surface of CD4 T-cells, the major HIV-1 target cell. There is strong evidence that binding between gp120, as part of a virion spike, and CD4 on cell surface is the first step for HIV entry into host cells. This multimeric CD4 provides a number of advantages over inhibitory CD4 molecules previously developed. First, this CD4 multimer is capable of binding at least 10 gp120 simultaneously with high avidity. Second, it does not enhance HIV infection at suboptimal concentrations, a phenomenon observed with previously developed recombinant CD4 molecules. Third, it has been demonstrated that this CD4 fusion protein hyper-crosslinks CD16 on natural killer (NK) cells and as a consequence delivers an exceptionally strong signal to NK cells, promoting potent Antibody-Dependent Cellular Cytotoxicity (ADCC) and lysis of HIV-infected cells. The inventors have shown that this recombinant CD4 multimer efficiently neutralizes primary isolates from different HIV subgroups.

The invention comprises an immunoglobulin construct having up to 12 amino terminal domains of CD4 (D1D2), the epitope responsible for HIV-1 gp120 binding activity. It also comprises domains of a human IgG1 heavy chain, as well as the IgA tailpiece that drives its polymerization. The two amino terminal domains of CD4 are fused to the CH2CH3 domains (which bears the FC receptor recognition epitopes) of a human IgG1 heavy chain. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this invention. Please contact William Ronnenberg at 301-451-3522 or wronnenberg@niaid.nih.gov for more information.

Prediction of Immune Response Outcomes to Keyhole Limpet Hemocyanin (KLH) Treatment

Tue, 27 Oct 2009 11:00:00 GMT
Keyhole limpet hemocyanin (KLH) is a large, heterogeneous glycosylated protein that is being tested as an immunotherapeutic agent to treat bladder cancer. KLH is approved for use in parts of Europe and Asia and is in late stage clinical trials in the U.S. KLH immunotherapy however only produces a clinical response in approximately 40-50% of patients, and currently there is no good method to select the subset of patients that will respond best to this treatment. This invention revealed that levels of certain serum antibodies can be used as biomarkers to predict the magnitude of the antibody response to the glycoprotein KLH. The best correlations are obtained by using a combination of markers. Since the size of the antibody response correlates with the clinical response, the invention provides a method to select the subset of patients that may benefit most from this form of treatment. CRADA Opportunity: The NCI Center for Cancer Research, Laboratory of Medicinal Chemistry, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a set of serum antibody-based biomarkers for personalized cancer immunotherapy using keyhole limpet hemocyanin (KLH). Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Novel Inhibitors of Interleukin-6 for Kaposi Sarcoma Therapy

Tue, 27 Oct 2009 15:00:00 GMT
The cancer therapy market is forecast to reach $40.9 billion by 2012. With immunosuppressant drugs set for phenomenal growth over the next six years, revenues could reach $26.2 billion by 2014. One market for which there is a significant need for new therapies is cancers induced by Kaposi Sarcoma-associated Herpesvirus (KSHV).

Researchers at the National Cancer Institute have identified novel nucleic acid sequences that act through a unique mechanism to inhibit the expression of interleukin-6 that occurs in cancerous cells transformed by KSHV infection and which promotes cancer cell proliferation. The researchers have also identified a key protein involved in the mechanism which could be inhibited using antibodies.

These inhibitors are likely to be accepted in the marketplace because their unique specificity in mechanism of action gives them a distinct advantage over the mechanisms of other existing therapies. CRADA Opportunity: The NCI Center for Cancer Research, HIV and AIDS Malignancy Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

B-cell Surface Reactive Antibodies for the Treatment of B-Cell Chronic Lymphocytic Leukemia

Mon, 12 Oct 2009 19:00:00 GMT
B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes. Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST). However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients. Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.

Available for licensing are fully human monoclonal antibodies that were selected from the first human post-alloHSCT antibody library. The library was generated from a time point after transplantation at which antibodies to B-CLL cell surface antigens peaked, thus indicating its therapeutic value. Utilizing phage display, the investigators generated a panel of fully human monoclonal antibodies that strongly bind to the same epitope on a B-CLL cell surface antigen. Weaker binding to normal B cells, but not to other lymphocytes, was observed. These fully human monoclonal antibodies provide readily available treatment that selectively targets malignant B cells. CRADA Opportunity: The Center for Cancer Research, Experimental Transplantation and Immunology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize fully human monoclonal antibodies selected from post-alloHSCT antibody libraries. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

A Target for the Development of Diagnostics and Therapeutics for Abnormal Hematopoiesis

Mon, 12 Oct 2009 23:00:00 GMT
The zinc finger protein ZFP36L2 has been shown by the inventors to play an essential role in hematopoiesis, a process that is dysregulated in hematological cancers, anemia, and other conditions. Thus, ZFP36L2 has promise for use in a diagnostic test to detect abnormal hematopoiesis, or as a target for the development of therapeutics to treat abnormal hematopoiesis.

Hematopoiesis is the formation of blood cellular components, through the differentiation of hematopoietic stem cells into lineages with a variety of roles, such as carrying oxygen, immune function, and blood clotting. Abnormally high hematopoiesis can be caused by hematological cancers such as leukemia or lymphoma, or by other myeloproliferative disorders. Abnormally low hematopoiesis can be caused by diseases such as anemia, thrombocytopenia, or myelodysplastic syndrome, and is often a secondary symptom of other conditions, such as cancer, infection, or dialysis.

The inventors have discovered that Zinc finger protein 36 like type-2 (ZFP36L2) plays an essential role in hematopoiesis, possibly by affecting the stability of mRNAs involved in this process. ZFP36L2 is a member of the tristetraprolin (TTP) family, which are mRNA-binding proteins involved in mRNA processing and degradation. The invention discloses methods of detecting abnormal hematopoiesis by detecting abnormal ZFP36L2 expression or a mutation in the ZFP36L2 gene, and methods of controlling abnormal hematopoiesis by modulating levels of ZFP36L2 protein. CRADA Opportunity: The NIEHS Laboratory of Signal Transduction, Polypeptide Hormone Action Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Elizabeth M. Denholm, Ph.D., Director, Office of Technology Transfer, NIEHS, at denholme@niehs.nih.gov for more information.

Susceptibility-Matched Multiwell Plates for MRI and NMR Spectroscopy

Tue, 13 Oct 2009 03:00:00 GMT
The technology is a patent estate covering multi-well assay plates for high-throughput screening using MRI and Nuclear Magnetic Resonance (NMR) spectroscopy. Conventional multi-well plates typically give poor performance for MRI-based assays since they provide inadequate matching of magnetic susceptibility between the plate, the sample and their surroundings. This results in distortion of the magnetic field within the scanner and reduces the sensitivity for detecting magnetic particles and the resolution of NMR spectra. The plates of this invention are a one-piece polyetherimide plastic construction for improved magnetic susceptibility matching for aqueous samples. Further, susceptibility matching can be achieved by including plugs, individually or as a cap mat, for each well the same plastic as the plate. The plates, with or without plugs, can be filled and manipulated by standard robotic laboratory equipment widely used in the pharmaceutical industry. Multi-well plates are used in high-throughput research applications such as clinical chemistry, immunology, and drug discovery. MR imaging of multi-well plates in particular offers the possibility of detecting magnetic nanoparticles for use as imaging agents. Moreover, MRI-guided localized NMR spectroscopy could be used to perform detailed chemical analysis of complex mixtures of metabolites not possible by conventional analytical techniques. Best of all, conventional MRI techniques exist which permit all samples in one or more multi-well plate(s) to be analyzed simultaneously. CRADA Opportunity: The National Institute on Aging, Magnetic Resonance Imaging & Spectroscopy Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Nicole Darack Guyton, Ph.D. at 301-435-3101 or guytonn@mail.nih.gov for more information.

Engineered Biological Pacemakers

Sat, 10 Oct 2009 07:00:00 GMT
A common symptom of many heart diseases is an abnormal heart rhythm or arrhythmia. While effectively improving the lives of many patients, implantable pacemakers have significant limitations such as limited power sources, risk of infections, potential for interference from other devices, and absence of autonomic rate modulation.

The technology consists of biological pacemakers engineered to generate normal heart rhythm. The biological pacemakers include cardiac cells or cardiac-like cells derived from embryonic stem cells or mesenchymal stem cells. The biological pacemakers naturally integrate into the heart. Their generation of rhythmic electric impulses involves coupling factors, such as cAMP-dependent PKA and Ca²⁺-dependent CaMK II, which are regulatory proteins capable of modulating/enhancing interactions (i.e. coupling) of the sarcoplasmic reticulum-based, intracellular Ca²⁺ clock and the surface membrane voltage clock, thereby converting irregularly or rarely spontaneously active cells into pacemakers generating rhythmic excitations. CRADA Opportunity: The National Institute on Aging, Cellular Biophysics Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Vio Conley at 301-496-0477 or conleyv@mail.nih.gov for more information.

Neutralization of Hepatitis C Virus (HCV)

Wed, 07 Oct 2009 11:00:00 GMT
Available for licensing and commercial development are compositions and methods for preventing and/or treating infection caused by hepatitis C virus (HCV). The invention is based on mapping studies conducted by the inventors of two epitopes within HCV E2: epitope I and epitope II. It has been discovered that epitope I is involved in virus neutralization but that epitope II mediates antibody interference, probably an adaptation of the virus to obfuscate the immune system. In an effort to attenuate or disable the interference effect of HCV-E2 epitope II, the present invention is directed to a HCV E2 polypeptide substitution/deletion of native amino acids LFY in epitope II, a HCV E2 polypeptide insertion of amino acids between the native LFY in epitope II, or the use of epitope II as a molecular decoyant or to affinity-purify an immune globulin to deplete interfering antibodies from, and enrich neutralizing antibodies in, the preparation. CRADA Opportunity: The FDA Center for Biologics Evaluation and Research, Laboratory of Plasma Derivatives, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Alice Welch, Ph.D. at 301-827-0359 or Alice.Welch@fda.hhs.gov for more information.

Novel Chemoattractant-Based Toxins to Improve Vaccine Immune Responses for Cancer and Infectious Diseases

Wed, 23 Sep 2009 15:00:00 GMT
Cancer is one of the leading causes of death in United States and it is estimated that there will be more than half a million deaths caused by cancer in 2009. A major drawback of the current chemotherapy-based therapeutics is the cytotoxic side-effects associated with them. Thus there is a dire need to develop new therapeutic strategies with fewer side-effects. Immunotherapy has taken a lead among the new therapeutic approaches. Enhancing the innate immune response of an individual has been a key approach for the treatment against different diseases such as cancer and infectious diseases.

This technology involves the generation of novel chemoattractant toxins that deplete the T regulatory cells (Treg) or other immunosuppressive or hyperactivated cells locally. Treg controls activation of immune responses by suppressing the induction of adaptive immune responses, particularly T cell responses. Immunosuppressive cells such as tumor infiltrating macrophages, regulatory T cells, regulatory B cells, or NKT and other cells down regulate antitumor immune responses. The chemoattractant toxins consist of a toxin moiety fused with a chemokine receptor ligand, such as chemokines and various chemoattractants, that enables specific targeting and delivery to the regulatory cells. This technology is advantageous over the more harmful antibodies and chemicals that are currently used for the systemic depletion of regulatory cells. The current technology can be used therapeutically in a variety of ways. They can be used together with vaccines to increase efficacy of the vaccine for the treatment of cancer, and can used to locally deplete Treg, Bregs, or other immuno suppressive cells to induce cytolytic cell responses at the tumor site or to eliminate chronic infectious diseases such as HIV and tuberculosis. CRADA Opportunity: The Immunotherapeutics Unit, National Institute on Aging, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Chemotoxin technology for clinical use or as a laboratory tool for depletion of cells. Please contact Nicole Darack, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information.

Bactericidal Peptides from Avian Leukocyte Ribonuclease A-2

Fri, 18 Sep 2009 19:00:00 GMT
These bactericidal polypeptides offer a novel alternative to conventional antibiotics that are used to treat and prevent bacterial infections. As infection-causing bacteria continue to develop antibiotic resistance to first line antibiotics there will always be a need for new antibiotic alternatives. Additionally, a greater understanding of the specific cytoxic activity of RNase A ribonucleases, their functional domains, and their roles in promoting anti-pathogen host defense may provide insight into new therapeutic agents.

This invention includes a novel RNase A ribonuclease from chicken leukocytes and polypeptides that have bactericidal activities against both gram positive and gram negative bacteria, including such pathogens as Escherichia coli, Salmonella spp., and Staphylococcus. CRADA Opportunity: The NIAID Laboratory of Allergic Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact William Ronnenberg, NIAID Office of Technology Development, at 301-451-3522 or wronnenberg@niaid.nih.gov for more information.

RNA Nanoparticles and Methods of Use

Fri, 18 Sep 2009 23:00:00 GMT
The invention hereby offered for licensing is in the field of nanoparticles and their usefulness in a variety of medical applications. More specifically the invention describes the design and synthesis of various RNA nanoparticles. These polyvalent nanoparticles comprise RNA motifs as building blocks that give the particles their unique characteristics. Moreover, the motifs can be pre-defined and chosen to give the particles desired characteristics (e.g. size and shape) tailored for a variety of applications. The polyvalent particles can utilize multiple unique positions to carry functional groups for cell recognition (e.g. cancer cells), therapy and detection. For therapeutic or detection applications the particles typically encompass at least two functional groups, a therapeutic or imaging agent and a targeting agent that will direct the particles to the targeted tissue.

RNA nanoparticles have the potential to serve as excellent drug or imaging delivery systems due to their designability and versatility. Furthermore, the RNA nanoparticles of the invention are also capable of self-assembly and potentially form nanotubes of various shapes which offer potentially broad uses in medical implants, gene therapy, nanocircuits, scaffolds and medical testing. CRADA Opportunity: The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize RNA nanostructures. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Osmogels: A New Method for Stabilizing Weak Molecular Complex Interactions

Sat, 19 Sep 2009 03:00:00 GMT
This invention describes a new method for stabilizing molecular complexes in polyacrylamide gels for analysis by the electrophoretic mobility shift assay. By adding specific osmolytes directly to the gel, investigators have found that weakly interacting molecular complexes can be sufficiently stabilized to allow quantitative analysis of the binding. Experiments with nonspecific labile complexes of two restriction endonucleases, EcoRI and BamHI, show that one of these added solutes is particularly effective at inhibiting complex dissociation, does not interfere with normal gel polymerization, and does not significantly slow normal gel migration. The results also demonstrate that sharp bands can be obtained for non-specific complexes of both enzymes on gels prepared with this solute while only smeared and distorted bands are observed on regular gels prepared without the solute. This method can be used for protein-protein, DNA-protein, and RNA-protein complexes, and can also be extended to include other techniques for separating complexes from free components using gel chromatography and capillary electrophoresis.

The potential market for gels that allow researchers to detect and quantify weak molecular complex interactions is significant; ranging from molecular biologists searching for novel regulatory DNA-binding proteins and convenient ways to detect protein-protein, or protein-DNA/RNA complexes to crystallographers needing reliable techniques to search for optimal conditions of complex formation. This technology has the potential to significantly impact biomedical research and development across many fields. CRADA Opportunity: The National Institute of Child Health and Human Development, Program in Physical Biology, Laboratory of Physical and Structural Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize osmogels for analysis of weak complexes by the electrophoretic mobility shift assay with potential extension of the technique to other separation methods. Please contact Joseph Conrad III, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information.

Mouse Embryonic Stem Cell-based Functional Assay to Evaluate Mutations in BRCA2

Thu, 17 Sep 2009 07:00:00 GMT
Mutations in breast cancer susceptibility genes BRCA1 and BRCA2 have up to an 80% life time risk in developing breast cancer. There are no “mutation hot spots” and to date, more than 1,500 different mutations have been identified in BRCA2. The absence of tumor cell lines expressing various mutant BRCA2 alleles has hindered evaluations to determine the functional differences between different mutations.

A simple, versatile and reliable mouse embryonic stem cell and bacterial artificial chromosome based assay to generate cell lines expressing mutant human BRCA2 has been developed and it has been used to classify 17 sequence variants. Available for licensing are a wild-type and eleven mutant BRCA2 cell lines developed from this assay that have either truncations or point mutations. These cell lines may be used to evaluate the effect of DNA damaging agents, genotoxins and chemotherapeutic efficacy. CRADA Opportunity: The Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize mouse embryonic stem cell lines suitable for functional analysis of BRCA2 variants. Please contact John Hewes, Ph.D. at hewesj@mail.nih.gov for more information.

Establishment of Two Cell Lines that Stably Express Luciferase for In Vivo Tracking

Thu, 17 Sep 2009 11:00:00 GMT
Available for licensing are two renal carcinoma cell lines, 786-O(luc) and 786-O/VHL/(luc) which both stably express luciferase. 786-O(luc) lacks von Hippel-Landau (VHL) protein expression and it has constitutively high expression of hypoxia-inducible transcription factor-2alpha (HIF-2alpha). The second stably expresses VHL, a tumor suppressor, and has minimal HIF-2apha expression. These cell lines can be tracked in vivo and can be used to study VHL-dependent and HIF-2apha dependent events such as tumorigenesis. VHL mutations lead to the clinical manifestations of von Hippel-Lindau disease, a rare autosomal dominant syndrome characterized by abnormal growth of blood vessels in multiple organs, including the brain and kidneys. CRADA Opportunity: The National Cancer Institute, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to develop further uses for these two cell lines that stably express luciferase for in vivo tracking. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Identification of Recent HIV-1 Infection by Genotypic Analysis for Treatment Strategy

Thu, 10 Sep 2009 15:00:00 GMT
This invention describes a bioinformatics algorithm capable of distinguishing between recently infected and chronically infected HIV-1 patients based on the genetic diversity of HIV pro-pol sequences. Directly after infection with HIV-1, genetic diversity is extremely low. Previously, single genome sequencing was used to demonstrate that HIV-1 genetic diversity accumulates after infection in a linear and predictable fashion during the first 8-10 months of infection (Kearney et al., 2009). Using single genome sequencing, it is possible to determine whether a person had been infected with HIV-1 in the recent past. Single genome sequencing is, however, a research technique that is relatively labor intensive and somewhat expensive, making it less feasible for routine use. The invention improves on this analysis in both ease and cost, and is capable of estimating genetic diversity using a population-based sequence that is obtained by routine, commercially available genotyping through the determination of genotype sequence ambiguity, which resulted in both sensitive and specific identification of acute versus chronic infection. The algorithm is also capable of simultaneously determining drug resistance profiles, further representing significant improvement over current antibody-based methods. Since recent data have shown that patients in the primary infection stage are estimated to be 26 times more infective than patients in the chronic stage of infection (Hollingsworth et al., 2008), and epidemiological models of immediate antiretroviral therapy (ART) predict a shift from the endemic phase to the elimination phase within five years (Granich et al., 2009), this invention represents a potentially valuable diagnostic tool for clinicians as well as an improvement over the current antibody-based methods of epidemiological research for determining HIV incidence. CRADA Opportunity: The NCI HIV Drug Resistance Program, Host Virus Interaction Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Therapeutic Antibacterial Applications of Phage

Thu, 03 Sep 2009 19:00:00 GMT
The NIH, in collaboration with others, has developed three groups of inventions related to the use of bacteriophages in therapeutic situations. The first group is a method of adapting phages to survive in the body substantially longer than wild-type phages, using serial passaging and/or genetic engineering. The second group involves phages designed to bind the toxins and cytokines that killed bacteria release into the bloodstream, reducing the pathogenic properties of the bacteria. The third group is a method of engineering a phage to have multiple binding sites, such that a single phage can target multiple types of bacteria. CRADA Opportunity: The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Rapid Diagnostic Applications of Phage

Thu, 03 Sep 2009 23:00:00 GMT
The NIH has available for licensing two techniques for rapid detection of a particular bacteria strain. Similar detection using currently available technologies take 1-2 days; this technology reduces the time to less than one hour. These technologies utilize phage, which has no pathogenic effect on higher plants and animals and are part of approved food-preparation formulations, indicating their known safety profile and an existing regulatory pathway. The first technique involves a phage that incorporates a reporter gene (e.g., luciferase) that will be expressed only when the phage successfully infects a bacterium. This technique is particularly useful where only bacteria-killing ("lytic") phages are known because the method also deactivates the lytic genes, enabling infection and subsequent detection. The second technique involves an engineered phage that will bind with quantum dots upon infection of bacteria; if a sample is treated first with this phage and then with quantum dots, the sample will only respond if the bacteria are present. Both techniques can be used to diagnose a clinical sample (tissue, blood, etc.) or an environmental isolate. CRADA Opportunity: The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Treatment of Airway Diseases, Including Asthma and COPD, by Targeting Airway Hyperresponsiveness

Thu, 03 Sep 2009 03:00:00 GMT
This technology provides methods of treatment for airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), utilizing molecules that target the airway hyperresponsiveness (AHR) pathway.

Airway diseases are a major health burden in the developed world. A major component of airway disease is airway hyperresponsiveness (AHR), defined as the exaggerated airway constrictive response to external triggers. The inventors have shown that inter-alpha-trypsin inhibitor (IaI), a mammalian protein involved in tissue inflammation and repair, is necessary for the development of AHR, and that inhibitors of IaI prevent the development of AHR. Specifically, the inventors tested their hypothesis that IaI inhibition or absence modifies airway smooth muscle cell binding to hyaluronan, a molecule known to contribute to the response to non-infectious lung injury, which also mediates induced AHR.

Claims in the provisional patent application are directed to methods of treating an airway disease or disorder by administering an inhibitor of IaI, such as an antibody, a polypeptide, a carbohydrate, a small molecule, or an antisense compound. CRADA Opportunity: The NIEHS Division of Intramural Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Dr. Elizabeth M. Denholm, Director of the Office of Technology Transfer, at denholme@niehs.nih.gov for more information.

Biomarkers for Sjogren's Syndrome

Wed, 02 Sep 2009 07:00:00 GMT
This technology provides differentially-expressed microRNAs that may be utilized for the development of diagnostics and therapeutics for Sjögren's syndrome.

Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the glands that produce tears and saliva. The hallmark symptoms of this disorder are dry mouth and dry eyes, but it can also cause serious complications throughout the body. Sjögren's syndrome affects as many as four million people in the United States, making it the second most common autoimmune rheumatic disease. Unfortunately, there is currently no cure for Sjögren's syndrome, nor is there a specific treatment to restore gland secretion. Treatment is generally symptomatic and supportive, including moisture replacement therapies and the use of non-steroidal anti-inflammatory drugs to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs are often prescribed, but these drugs can have serious side effects.

The inventors have identified microRNAs that are differentially expressed in patients with Sjögren's syndrome compared to the normal population; these biomarkers can be used to diagnose Sjögren's syndrome, and are potential targets for treatment of this disease. The inventors have also identified microRNAs associated with high or low salivary flow in this patient population; these markers may serve as targets for therapeutics that restore salivary flow. CRADA Opportunity: The NIDCR is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize differentially-expressed microRNAs. Please contact David Bradley at bradleyda@nidcr.nih.gov.

Immunogenic Tumor-associated Antigen SPANX-B for Selective Cancer Immunotherapy

Wed, 02 Sep 2009 11:00:00 GMT
Researchers at the National Institutes of Health (NIH) have characterized a novel tumor-associated antigen, SPANX-B, that is naturally immunogenic and is expressed in a variety of human malignancies, including melanoma and lung, colon, renal, ovarian and breast carcinomas. In melanoma specifically, SPANX-B expression is associated with advanced and metastatic disease. Moreover, the researchers have found several agonist epitope peptides from SPANX-B which can be used to activate the immune system to eradicate tumors utilizing T cells. SPANX-B peptides have significant clinical and immunotherapeutic potential for the development of cancer diagnostic assays and potent protective and/ or therapeutic vaccines to combat a wide-range of cancers. CRADA Opportunity: The National Institute on Aging, Laboratory of Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of SPANX-B-based therapeutic approaches to combat cancers. Please contact Nicole Guyton, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information.

Monoclonal Antibodies That React With the Capsule of Bacillus anthracis

Mon, 31 Aug 2009 15:00:00 GMT
Bacillus anthracis is the causative agent of anthrax and is surrounded by a polypeptide capsule of poly-gamma-D-glutamic acid (gammaDPGA). gammaDPGA is poorly immunogenic and has antiphagocytic properties. The bacterial capsule is essential for virulence. Antibodies to the capsule have been shown to enhance phagocytosis and killing of encapsulated bacilli. These antibodies in combination with antibodies that neutralize the toxins of B. anthracis could provide enhanced protection by their dual antibacterial and antitoxic activities. Such antibodies would be especially useful for antibiotic-resistant strains.

In order to obtain therapeutically useful anti-gamma DPGA monoclonal antibodies (MAbs), the inventors immunized chimpanzees with conjugates of 15-mer glutamic acid polymers to immunogenic protein carriers (recombinant protective antigen (PA) of B. anthracis). After several immunizations, chimpanzees developed strong immune responses to gammaDPGA. A combinatorial Fab library of mRNA derived from the chimpanzee's bone marrow was prepared and eight (8) distinct Fabs reactive with native gammaDPGA were recovered. Two (2) of the Fabs were converted into full-length IgG with human gamma1 heavy chain constant regions. These two (2) MAbs showed strong opsonophagocytic killing of bacilli in an in vitro assay. These two (2) MAbs were also tested for protection of mice challenged with virulent anthrax spores and results showed that both MAbs provided full or nearly full protection at a dose of 0.3 mg, the lowest dose tested, which is much more potent than previously reported murine anti-PGA MAbs. Since chimpanzee immunoglobulins are virtually identical to human immunoglobulins, these chimpanzee anticapsule MAbs may have clinically useful applications.

This application claims the antibody compositions described above. Also claimed are methods of treating or preventing B. anthracis infection in a mammalian host and isolated polynucleotides comprising a nucleotide sequence encoding the antibodies of the technology. CRADA Opportunity: The NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MAbs neutralizing anthrax toxins and capsule for comprehensive protection against anthrax. Please contact Bill Ronnenberg, NIAID Office of Technology Development, at 301-451-3522 for more information.

Antigenic Chimeric Tick-Borne Encephalitis Virus/Dengue Virus Type 4 Recombinant Viruses

Mon, 31 Aug 2009 19:00:00 GMT
The tick-borne encephalitis virus (TBEV) complex is a group of viruses that can cause severe neutrotropic disease and up to thirty percent (30%) mortality. While these viruses can be found in many parts of the world, the largest impact of the disease occurs in Europe and Russia, where approximately fourteen thousand (14,000) hospitalized TBEV cases occur annually. TBEV is in the family Flaviviridae, genus flavivirus and is composed of a positive-sense single stranded RNA genome that contains 5' and 3' non-coding regions and a single open reading frame encoding ten (10) proteins. At present, a vaccine or FDA approved antiviral therapy is not available.

The inventors have previously developed a WNV/Dengue4Delta30 antigenic chimeric virus as a live attenuated virus vaccine candidate that contains the WNV premembrane and envelope (prM and E) proteins on a dengue virus type 4 (DEN4) genetic background with a thirty nucleotide deletion (Delta30) in the DEN4 3'-UTR. Using a similar strategy, the inventors have generated an antigenic chimeric virus, TBEV/DEN4Delta30. This chimeric virus also contains attenuating mutations within the E and nonstructural NS5 proteins. Preclinical testing results with the derived virus indicate that chimerization of TBEV with DEN4Delta30 and introduction of the attenuating mutations decreased neuroinvasiveness and neurovirulence in mice. The TBEV/DEN4delta30 vaccine candidate was safe, immunogenic, and provided protection in monkeys against challenge with TBE viruses.

This application claims live attenuated chimeric TBEV/DEN4Delta30 vaccine compositions. Also claimed are methods of treating or preventing TBEV infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a TBEV immunogen, methods for detecting TBEV infection in a biological sample and infectious chimeric TBEV. CRADA Opportunity: The NIAID is seeking statements of capability or interest from parties interested in collaborative research in preclinical study of the long-term immunity induced by the TBEV/DEN4 vaccine candidate against highly virulent TBE viruses and in the clinical trials of this vaccine in humans. Please contact Maryann Puglielli, NIAID Office of Technology Development, at 301-496-2644 for more information.

Superior Method of Preparing Dendrimers for Use as Magnetic Resonance Imaging (MRI) Contrast Agents

Tue, 11 Aug 2009 23:00:00 GMT
There is a need to develop more efficient gadolinium-containing (Gd) contrast agents for magnetic resonance imaging (MRI) as the small molecules presently used clinically have the disadvantage of being rapidly cleared from circulation and excreted by the kidneys.

Dendrimer-based macromolecular MRI contrast agents in which numerous chelated Gd ions are covalently attached to a multivalent dendritic architecture are a promising class of diagnostic agents for medical imaging applications. Clinical development of the dendrimer-based agents has been limited as the current methods for synthesizing them result in a complex mixture that produces inconsistent imaging results.

The present technology describes the development of a new method of pre-forming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. Specifically, for example, a 1B4M-DTPA-Gd chelate is preformed in methanol and purified prior to conjugation to a PAMAM dendrimer molecule. This results in a dendrimer-based MRI contrast agent with greatly improved homogeneity and stability, and possessing an unexpectedly greater molar relaxivity that allows the use of much less of the agent than previously required to obtain comparable images. The use of a DOTA-Gd chelate is equally possible. CRADA Opportunity: The Inorganic & Radioimmune Chemistry Section, ROB, CCR, NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize macromolecular (dendrimer-based) MR contrast agents as well as multi-modality analogs. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Multilayered RF Coil System for Improving Transmit B1 Field Homogeneity in High-Field MRI

Wed, 12 Aug 2009 03:00:00 GMT
Available for licensing and commercial development is a multilayered radio-frequency (RF) coil system for improving the transmit B1 field homogeneity for magnetic resonance imaging (MRI) at high field strengths. The current invention aims at manipulating the inhomogeneous profile of the transmit B1 field, which causes MR images to become less uniform as the magnetic field strength is increased, by utilizing an inner array of RF elements (e.g. surface coils) within and coupled to an outer transmit unit (e.g. a birdcage coil or other volume coil). Improvement in B1 field homogeneity is achieved by tuning the surface coils of the inner layer to an appropriate resonant frequency and then passively coupling them to the outer-layer volume coil. Furthermore, the amount of coupling is determined by the intrinsic properties of the transmit unit and can be adjusted accordingly. The current design provides an effective approach for reducing B1 field homogeneity at high fields and can be implemented without the need for independent RF channels, thereby reducing MRI system complexity. Furthermore it can be readily implemented on existing MRI coil systems by detuning surface coils rather than decoupling them during the transmit phase. CRADA Opportunity: The Laboratory of Functional and Molecular Imaging (LFMI) at the National Institute of Neurological Disorders and Stroke (NINDS) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MRI applications that aim to provide novel functional and molecular imaging techniques to study brain structure and function. Please contact Melissa Maderia, Ph.D. at maderiam@mail.nih.gov or 301-451-3943 for more information.

Oligo Microarray for Detection of All Known Mammalian and Avian Pathogenic Viruses

Tue, 11 Aug 2009 07:00:00 GMT
The spectrum of pathogenic viruses of importance in human disease, agriculture and biology is not only large and diverse, but continually evolving. The identification or isolation of viral pathogens, in correlation with the presence of specific disease phenotypes, is of paramount importance both to diagnosis of disease and the subsequent management or treatment of viral infection. The limitations of current viral detection methods, such as PCR and immunoassays, led to the development of a novel microarray system for specific detection of viruses. The technology offered here for licensing provides a method for high-throughput screening of known pathogenic viruses along with identification of "new" disease-associated viruses.

The novel method is based on a viral microarray containing 10,000 immobilized DNA oligonucleotide features, representing all known mammalian and avian pathogenic viruses (approximately 600). Software was also developed to analyze the viral microarray results. The oligonucleotide features in this system are 60-mer long and distributed across both conserved and non-conserved regions of known viral sequences. This design serves the dual purpose of: (1) facilitating validation via redundant signals associated with each represented virus and (2) allowing for the discovery of new viruses, which arise due to recombination. In addition, positive and negative controls against human and mouse housekeeping genes are included along with software for analysis of virus microarray results.

Further advantages of the viral microarray include: (a) the use of sample inputs as little as 10ng of either total DNA or RNA extracted from virus infected cells, representing as few as 20 viral particles; (b) detection of viruses of both DNA and RNA classes; (c) a capacity for high-throughput screening of various sample types including serum, saliva and biopsy tissues; and (d) analysis of a large number of samples in parallel on identical arrays.

The detection of viral DNA is unique to this technology, as other available technologies only detect viral genomic RNA or viral mRNA transcripts. Additionally, the viral chip was found to be highly specific and sensitive for detecting different viral genomic sequences in cell lines and multiple viral constructs co-infection in cultured cells. CRADA Opportunity: The NCI Laboratory of Molecular Technology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this oligo microarray for identification and detection of all known mammalian and avian pathogenic viruses. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Methods for Treating or Ameliorating Fibrosis by Inhibiting the Interaction between IL-21 Receptor (IL-21R) and IL-21

Wed, 29 Jul 2009 11:00:00 GMT
This invention includes methods for treating or ameliorating fibrosis by inhibiting the interaction between IL-21 Receptor (IL-21R) and IL-21 using either anti-IL-21R monoclonal antibodies (or binding fragments of anti-IL-21R mAbs), anti-IL-21 monoclonal antibodies (or binding fragments of anti-IL-21 mAbs) or soluble IL-21R (or binding fragments of IL-21R). It is believed that the TH2 immune response, induced by IL-21, plays a major role in the in the pathogenesis of tissue fibrosis. Antagonism of IL-21R by anti-IL-21R monoclonal antibodies or the sequestration of IL-21 by soluble IL-21R or anti-IL-21 monoclonal antibodies has been demonstrated to reduce TH2 immune responses associated with fibrosis in animal models.

The causes of chronic tissue fibrosis are diverse and the market for a therapeutic that targets fibrosis is large. Fibrosis is associated with diverse causes which include: genetic diseases (such as cystic fibrosis); autoimmune diseases (such as scleroderma); chronic viral infections (such as hepatitis), parasitic infections (such as schistosomiasis); and occupational exposures to causative agents (such as asbestosis). Additionally, many cases of tissue fibrosis are idiopathic. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this invention. Please contact Nicole Mahoney at 301-435-9017 or mahoneyn@niaid.nih.gov for more information.

Treatment of Cancer Using Metal Coordinating Compounds that Kill Multi-Drug Resistant Cancer Cells

Wed, 29 Jul 2009 15:00:00 GMT
One of the major hindrances to successful cancer chemotherapy is the development of multi-drug resistance (MDR) in cancer cells. MDR is frequently caused by the increased expression or activity of ABC transporter proteins in response to the toxic agents used in chemotherapy. Research has generally been directed to overcoming MDR by inhibiting the activity of ABC transporters. However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects, restricting their usefulness as therapeutics.

In an alternative approach to reducing the debilitating effects of MDR during cancer therapy, scientists at the NIH have identified a family of compounds whose activities are enhanced, rather than decreased, in MDR cancer cells. Particular embodiments of these "MDR-selective compounds" include certain metal coordinating compounds. Recent evidence suggests that these MDR-selective compounds can be used to kill cancer cells that overexpress ABC transporters or to re-sensitize multi-drug resistant cancer cells to chemotherapeutics. Furthermore, the effectiveness of these compositions in killing MDR cancer cells correlates directly with the level of ABC transporter expression. Importantly, MDR-selective compounds are not inhibitors of ABC transporters, thereby reducing the likelihood of undesirable side-effects during treatment. Thus, MDR-selective compounds represent a powerful strategy for treating multi-drug resistant cancers as a direct chemotherapeutic and as agents that can re-sensitize MDR cancer cells for treatment with additional chemotherapeutic agents. CRADA Opportunity: The Institute of Enzymology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MDR-selective compounds. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Truncated Methanocarba Adenosine Derivatives as A₃ Adenosine Receptor Antagonists

Wed, 29 Jul 2009 19:00:00 GMT
Novel A₃ adenosine antagonists available for licensing. A₃ receptors are particularly highly expressed in inflammatory cells, making it a potentially desirable target for inflammatory diseases. This technology relates to highly specific antagonists and partial agonists of A₃ adenosine receptors, which are negatively coupled to adenylate cyclase and have been broadly implicated in inflammation, cardiovascular disease, and cancer. Further, A₃ adenosine receptors have been implicated in allergies, asthma, and chronic obstructive pulmonary disease. CRADA Opportunity: The NIDDK, Laboratory of Bioorganic Chemistry is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize A₃ adenosine receptor antagonists. Please contact Kenneth A. Jacobson, Ph.D. at kajacobs@helix.nih.gov or the NIDDK Office of Technology Transfer and Development at 301-451-3636 for more information.

A Tumorigenic MEF/3T3 Tet-Off Mouse Fibroblast Cell Line Stably Transfected with a T7-Tagged Srp20 Expression Construct (pJR17)

Wed, 29 Jul 2009 23:00:00 GMT
Alternative RNA splicing is a means by which the human genome can produce many more proteins from the genes available. It is emerging that aberrations in alternative RNA splicing contributes to the development of cancers. SRp20 is a cellular splicing factor that is involved in the process of alternative splicing of RNA. Investigators at the National Cancer Institute (NCI), National Institutes of Health (NIH) have discovered that SRp20 is overexpressed in many types of cancer and furthermore promotes the induction and maintenance of tumor cell growth. This was demonstrated in part by engineering a non-tumorigenic cell to become tumorigenic in mice by overexpressing SRp20.

Research Material available for licensing is a tumorigenic MEF/3T3 tet-off mouse fibroblast cell line stably transfected with a T7-tagged SRp20 expression construct (pJR17) that is under the transcriptional control of tetracycline. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, HIV and AIDS Malignancy Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize A Tumorigenic MEF/3T3 Tet-Off Mouse Fibroblast Cell Line Stably Transfected with a T7-Tagged Srp20 Expression Construct (pJR17). Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

High-yield Methods of Producing Biliverdin

Thu, 30 Jul 2009 03:00:00 GMT
This invention describes methods of making high yields of biliverdin, the pharmaceutical compositions of biliverdin made using that process, and methods of using the compositions therapeutically.

In reaction to a wide range of cellular stresses, hemoglobin is naturally metabolized to biliverdin, which is then quickly metabolized to bilirubin, a bile pigment, through a highly conserved set of enzymes. Both bilirubin and biliverdin are normally processed for rapid excretion, and excessive serum levels of bilirubin have known toxic effects (most notably jaundice). Surprisingly, research in the past decade has shown that decreasing serum levels correlate inversely with the prognosis of various disorders, such as ischemia/reperfusion injuries, atherosclerosis, organ transplantation, and several autoimmune diseases. Indeed, in animal-model studies, inducing a mild case of jaundice actually improved outcome. Unfortunately, bilirubin is relatively insoluble, and so is not a practical pharmaceutical itself.

Biliverdin has lower direct toxicity and substantially greater solubility than bilirubin, and also appears to have some direct therapeutic effects similar to bilirubin. Accordingly, biliverdin has been widely studied lately. Generating high yields of pure biliverdin is difficult, however, because any system with the enzymes to break down hemoglobin also has enzymes converting biliverdin to bilirubin. The inventors have created a system of generating microorganisms (yeast) lacking the enzymes that break biliverdin down to bilirubin. CRADA Opportunity: The Laboratory of Pathology in the Center for Cancer Research of the National Cancer Institute is seeking parties interested in collaborative research directed toward clinical applications of biliverdin. For more information about the research, please contact either Dr. Michael Pendrak (NCI/CCR Laboratory of Pathology) at (301) 496-6264, or Dr. April Franks (NCI Technology Transfer Center) at (301) 496-0477.

Mouse Monoclonal Antibody Targeting Tetanus Toxin Heavy Chain Fragment C

Tue, 14 Jul 2009 07:00:00 GMT
The FDA is pleased to announce as available for licensing a murine monoclonal antibody that specifically binds to Fragment C of tetanus toxin. Tetanus toxin is one of the most potent neurotoxins known. It is a complex molecule, composed of a linked heavy chain and light chain, each having different domains serving different functions. One domain of the heavy chain, known as "Fragment C," is known to bind the toxin to neurons. Fragment C is the focus of much research, including: analysis of the subtle differences between neuronal uptake of tetanus toxin and the related botulinum toxin, the design of compounds that block the uptake of tetanus toxin, and design of drugs that target the same cellular mechanism to enhance uptake. CRADA Opportunity: The FDA's Office of Biotechnology Products in the Center for Drug Evaluation and Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antibodies directed against tetanus toxin. Please contact Alice Welch, Ph.D. at 301-827-0359 or Alice.Welch@fda.hhs.gov for more information.

High Diversity/High Affinity Domain Antibody Library

Tue, 14 Jul 2009 11:00:00 GMT
Available for licensing and commercial development is a highly diverse domain antibody (dAb) library providing antibodies that bind with high affinity to variety of antigen targets. Antibody diversity is inherently limited by using only three CDRs of either light chain variable domain (LCDRs) or heavy chain variable domain (HCDRs). This novel dAb library is designed using light chain variable domain 3 (LCDR3) and heavy chain variable domain (HCDR3), which are of primary importance for creating binding site diversity in the human immune system. The library contains 2.5 x 10¹⁰ dAbs. Human naturally occurring LCDR3s were grafted onto HCDR1 of m0. These antibodies are of very small size (15-17 kDa), high stability and can be expressed at high levels as monomers. The library can be used for the selection of antibodies to any antigen including cancer and viral antigens and exhibit such properties as good penetration, stability, solubility, high levels of expression (at potentially low cost), and low level of immunogenicity or toxicity. CRADA Opportunity: The National Cancer Institute, CCR, CCRNP is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this domain antibody library. Please contact John Hewes, Ph.D. at hewesj@mail.nih.gov for more information.

Novel Dopamine Receptor Ligands as Therapeutics for Central Nervous System Disorders

Wed, 08 Jul 2009 15:00:00 GMT
The dopamine D3 receptor subtype is a member of the dopamine D2 subclass of receptors. These receptors have been implicated in a number of CNS disorders, including psychostimulant abuse, psychosis and Parkinson's disease. Compounds that bind with high affinity and selectivity to D3 receptors can not only provide important tools with which to study the structure and function of this receptor subtype, but may also have therapeutic potential in the treatment of numerous psychiatric and neurologic disorders.

The 4-phenylpiperazine derivatives are an important class of dopamine D3 selective ligands. However, due to their highly lipophilic nature, these compounds suffer from solubility problems in aqueous media and reduced bioavailability. To address this problem, a process was designed to introduce functionality into the carbon chain linker of these compounds. Compared to currently available dopamine D3 receptor ligands, the resulting compounds show improved pharmacological properties and D3 selectivities but due to their more hydrophilic nature, these derivatives are predicted to have improved water solubility and bioavailability. CRADA Opportunity: The National Institute on Drug Abuse's Medications Discovery Research Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize 4-phenylpiperazine derivatives as dopamine D3 selective ligands. Please contact VioConley, M.S. at 301-435-2031 or conleyv@mail.nih.gov for more information.

Therapeutic Applications of a p53 Isoform in Regenerative Medicine, Aging, and Cancer

Thu, 02 Jul 2009 19:00:00 GMT
p53 plays a critical role in carcinogenesis and aging as a key regulator of cell cycle progression, senescence and apoptosis. The inventors have discovered that a natural variant of p53 (delta133p53) inhibits p53-dependent cell senescence. Utilizing delta133p53 siRNAs, the inventors have data demonstrating that siRNA-treated human fibroblast undergo cell senescence, thereby indicating that delta133p53 inhibition could be a novel approach for cell senescence-mediated anti-proliferative therapy, including anti-cancer treatments. Alternatively, enhanced expression with delta133p53 can extend the replicative lifespan of normal human cells. This technology may provide a new method in the field of regenerative medicine for aging-related degenerative disease.

Also available for licensing are delta133p53 siRNAs and shRNA vectors, as well as a delta133p53 overexpression vector, which can be used for cancer and age-related degenerative therapeutics. The shRNA can be stably integrated into the cellular genome for long-term delta133p53 inhibition.

The inventors have also discovered that another p53 variant (p53beta) accelerates p53-dependent cell senescence, and developed a vector for overexpressing p53beta, which could be used for cell senescence-mediated anti-proliferative therapy. CRADA Opportunity: The National Cancer Institute, Laboratory of Human Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Curtis_Harris@nih.gov for more information.

Gene Expression Signature Predictive of Response to Chemotherapy

Thu, 02 Jul 2009 23:00:00 GMT
Combination cisplatin and fluorouracil (CF) is a reference chemotherapy regimen for metastatic gastric cancer. However, to date, no genome-wide studies have identified distinctions in gene expression that predict which subjects with metastatic disease will benefit from this therapy and which subjects will not exhibit a therapeutic response to chemotherapy. Given the toxicity of chemotherapy, however, defining parameters that identify those subjects who will likely benefit from chemotherapy is of paramount importance. Early identification of non-responders would provide opportunities to explore alternate or novel therapeutic approaches. Thus, a need exists to identify methods of predicting a subject's response to chemotherapy prior to receiving the treatment.

Scientists at the National Institutes of Health have discovered a three-gene signature that can be used to determine the chemotherapy response in patients with cancer. By measuring the expression of three cancer-specific genes it can be determined if a patient with an epithelial cancer such as gastric, bladder, head and neck, esophageal or cervical cancers, will respond to CF treatment. The inventors have demonstrated that examining these expression levels has high fidelity in identifying CF treatment non-responders. Further, the invention describes a mechanism that can help patients identified as non-responders become responsive to treatment. Therefore these methods have the potential to reduce fatalities caused by metastatic gastric cancer by identifying patients early on who are non-responsive to standard CF treatment and customizing a new treatment plan which may be better suited to their individual needs. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Laboratory of Cancer Biology and Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Gene Expression Signature Predictive of Response to Chemotherapy. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Immunogenic Peptide from NGEP Protein for Developing Prostate Cancer Vaccines

Fri, 03 Jul 2009 03:00:00 GMT
The NGEP protein is only present in the prostate and is typically overexpressed on prostate cancer cells. Hence, as a novel prostate tumor-associated antigen (TAA) it is a good target for developing active immunotherapies to kill prostate cancer cells. For example, NGEP could be used in a vaccine to activate an individual's immune system to recognize and kill NGEP-expressing prostate cancer cells. However, TAAs typically are not very effective in inciting an immune response. This can be overcome by identifying portions (epitopes) of the TAA that are more immunologically active.

Investigators at the NIH have identified a small peptide fragment of the NGEP protein (NGEP CTL peptide epitope) that is very effective in activating cytotoxic lymphocytes causing them to destroy prostate cancer cells and has great potential for development of a variety of active immunotherapy strategies, such as vector-based cancer vaccines, to treat and prevent prostate cancer. In addition, it could be used for developing sensitive immunoassays for measuring the immune response of a prostate cancer patient during immunotherapy. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Laboratory of Tumor Immunology and Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Kevin Brand, J.D. at 301-451-4566 or brandk@mail.nih.gov for more information.

The Protein Cyanovirin Inactivates HIV and Influenza

Thu, 02 Jul 2009 07:00:00 GMT
Cyanovirin-N (CV-N) potently and irreversibly inactivates diverse primary strains of HIV-1, including M-tropic forms involved in sexual transmission of HIV, as well as T-tropic and dual-tropic forms. CV-N also blocks cell-to-cell transmission of HIV infection. CV-N interacts in an unusual manner with the viral envelope, binding with extremely high affinity to poorly immunogenic epitopes on gp120. Further, CV-N and homologous proteins and peptides potently inhibit diverse isolates of influenza viruses A and B, the two major types of influenza virus that infect humans.

The described technology includes glycosylation-resistant mutants, which code sequences to enable ultra large-scale recombinant production of functional CV-Ns in non-bacterial (yeast or insect) host cells or in transgenic animals or plants. Therefore, these glycosylation-resistant mutants may allow industry to produce CV-Ns on a large scale and make CV-Ns cheap enough for developing countries to benefit from this invention.

CV-N was benign in vivo when tested in the rabbit/monkey vaginal toxicity/irritancy model and was not cytotoxic in vitro against human immune cells and lactobacilli. CV-N is readily soluble in aqueous media, is remarkably resistant to physicochemical degradation and is amenable to very large-scale production by a variety of genetic engineering approaches. CRADA Opportunity: The National Cancer Institute, Molecular Targets Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Modulators of Pregnane X Receptor (PXR) as Therapeutics for Bowel Disorders (BD)

Thu, 02 Jul 2009 11:00:00 GMT
This technology is based on the novel findings that susceptibility to BD is strongly associated with genetic variation in the PXR gene, a member of the nuclear receptor family, and rifaximin is a specific activator of human PXR. PXR is an integral component of the body's defense mechanism involved in endogenous and xenobiotic detoxication. Based on these novel findings, the present technology provides a) methods of screening for compositions that modulate inflammatory bowel disease (IBD), b) methods of inhibiting inflammation of the bowel and related tissues and organs, and c) methods of treatment of inflammatory bowel disease. CRADA Opportunity: The Laboratory of Metabolism, Center for Cancer Research, NCI, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize compounds that ameliorate bowel disorders through the PXR pathway. Please contact Lisa Finkelstein, Ph.D. at 301-451-7458 or lfinkels@mail.nih.gov for more information.

A Locking Device for Permanently Securing Surgical Suture Loops

Thu, 02 Jul 2009 15:00:00 GMT
This technology relates to a device that can be used to non-invasively secure surgical suture loops when combined with a percutaneous delivery system. It has been shown to be effective in correcting mitral valve regurgitation (MVR) in an animal model. During the procedure, a guidewire is percutaneously conveyed to the atrium of the heart and is used to secure the "cerclage" suture encircling the mitral valve annulus, which is delivered using a delivery catheter. The locking device is advanced over the suture by the delivery catheter and it permanently secures the suture and maintains the tension on the annulus once the delivery system is removed. This locking device, in combination with the percutaneous procedure, allows for more complete coaptation of the valve leaflets and correction of MVR without the need for open heart surgery and its associated risks. The locking device is also adjustable, allowing the user to vary the tension on the suture if further tightening or loosening is required. It is also MRI compatible and all follow-up studies can be performed under MRI.

This invention has demonstrated its ability to correct MVR in animals where the locking device was observed to maintain the correct position and tension after implantation. This device has the potential to replace the traditional loop and knot method used for surgical correction of MVR, and may also be useful for other conditions that require permanently secured suture loops. CRADA Opportunity: The National Heart Lung and Blood Institute Cardiac Catheterization Lab is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the tension fixation device. Please contact Peg Koelble at 301-594-4095 or koelblep@nhlbi.nih.gov for more information.

Novel Compounds that Specifically Kill Multi-Drug Resistant Cancer Cells

Thu, 02 Jul 2009 19:00:00 GMT
One of the major hindrances to successful cancer chemotherapy is the development of multi-drug resistance (MDR) in cancer cells. MDR is frequently caused by the increased expression or activity of ABC transporter proteins in response to the toxic agents used in chemotherapy. Research has generally been directed to overcoming MDR by inhibiting the activity of ABC transporters. However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects, restricting their usefulness as therapeutics.

Investigators at the NIH previously identified that the compound NSC73306 had the ability to specifically kill cancer cells that overexpressed an ABC transporter responsible for MDR. Importantly, this "MDR-selective compound" is not an inhibitor of ABC transporters, reducing the likelihood of undesirable side-effects if used as a therapeutic.

Using NSC 73306 as a model, new MDR-selective compounds have been created with improved solubility and selectivity. These new MDR-selective compounds can also selectively kill MDR cancer cells, with their efficacy correlating directly with the level of ABC transporter expression. Recent evidence also shows that these new MDR-selective compounds have the ability to decrease the expression of ABC transporters, potentially re-sensitizing the cancer cells to chemotherapeutic agents. Thus, MDR-selective compounds represent a powerful strategy for treating multi-drug resistant cancers as a direct chemotherapeutic and as agents that can re-sensitize MDR cancer cells for treatment with additional chemotherapeutic agents. CRADA Opportunity: The National Cancer Institute, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the agents described here. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Differentiation of Human Embryonic Stem Cells into Dopaminergic Nerve Cells

Tue, 23 Jun 2009 23:00:00 GMT
The invention described here is a novel method of differentiating human embryonic stem cells (hESCs) into dopaminergic nerve cells, which is preferable to the currently available dopaminergic differentiation techniques.

This invention potentially provides a source of sufficient dopaminergic cells not only for the clinical transplantation of dopaminergic tissue but also for in vitro studies of human cells useful for pharmaceutical screens related to neurodegenerative disorders and substance abuse.

Neurodegenerative disorders encompass a range of debilitating conditions including Parkinson's disease, Alzheimer's disease, and Huntington's disease. The primary cause of cognitive dysfunction for these three disorders has been directly linked to neuron degeneration, usually in specific areas of the brain. Transplantation of fetal dopaminergic neurons in affected areas of the brain in late stage Parkinson's disease has demonstrated clinical utility in human patients. However, fetal transplantation therapy generally requires human tissue from at least 3-5 embryos to obtain a clinically reliable improvement in the patient, thus demonstrating a need for a larger and more reliable source of dopaminergic cells. HESCs are a promising alternative source of cells because they can grow in culture indefinitely and have the ability to differentiate into a variety of cell types. One of the most efficient methods for conversion of hESCs to dopaminergic neurons requires the presence of mouse stromal cells which have an undefined dopaminergic inducing activity. However, the major disadvantage of this method is the exposure of hESC to mouse cells, which hinders any downstream clinical application due to possible transfer of animal cells and pathogens. This invention has unveiled the molecular nature of the activity of the mouse cells and established an efficient alternative approach for dopamine neuron generation, which is more suitable for clinical application. This innovative approach potentially provides a large and reliable source of dopaminergic cells sufficient for clinically relevant transplantation of dopaminergic tissue as well as in vitro pharmacologic studies of human dopaminergic cells. CRADA Opportunity: The National Institute on Drug Abuse, Development and Plasticity Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Vio Conley, M.S. at 301-496-0477 or conleyv@mail.nih.gov for more information.

Inflammatory Genes and MicroRNA-21 as Biomarkers for Colon Cancer Prognosis

Wed, 24 Jun 2009 03:00:00 GMT
Colon adenocarcinoma is the leading cause of cancer mortality world-wide and accounts for approximately 50,000 deaths annually in the United States. Adjuvant therapies improve survival for stage III colon cancer patients; however, it remains controversial if stage II patients should be given these therapies. Some stage II patients will benefit from therapy (such as patients with undetectable micro-metastases where surgery will not be curative); but therapy for others will harm quality of life with little therapeutic benefit (such as patients where surgery removed all cancerous tissue and therefore do not need additional therapy). Thus, there is a need to for biomarkers capable of accurately identifying high risk, stage II patients that are suitable for therapeutic intervention.

The investigators have identified an inflammatory gene and microRNA biomarker portfolio that can predict aggressive colon cancer, colon cancer patient survival, and patients that are candidates for adjuvant therapy. These biomarkers provide clinicians with a powerful tool to diagnose colon cancer patients and chose effective treatment methods. CRADA Opportunity: The NCI Laboratory of Human Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cancer biomarkers and therapeutic targets. Please contact Curtis_Harris@nih.gov for more information.

A Novel System for Producing Infectious Hepatitis C Virus (HCV) Virions and Development of a Novel Reporter System for Studying HCV Entry

Tue, 23 Jun 2009 07:00:00 GMT
HCV has infected an estimated 3% of the world population in whom viral infection persists for more than two third of the cases, often resulting in life-threatening complications. The standard of care (pegylated interferon alpha-2 plus ribavirin) is efficient in only 50% of treated patients, costly and has numerous side effects. In addition, viral resistance to newly developed drugs -- targeting viral protease or RNA polymerase -- has been described, but no vaccine is yet available. The difficulty in developing HCV vaccines is largely due to the broad sequence-diversity displayed by HCV, the frequent occurrence of viral mutations within immunogenic epitopes in vivo, and the lack of proper standard/definition for viral neutralization.

One alternative strategy in HCV-vaccine or drug development comprises measuring viral entry, the first step in viral infection. Such measurements are limited by the available screening systems, in that, HCV pseudo-typed retroviral particles have a different envelope conformation and contain foreign components that are likely to interfere with the measured HCV entry. Moreover, HCV lab strain requires intensive replication for its in vitro production, resulting in numerous mutations that impede development of convenient screening tools.

The inventors have developed a system for generating infectious HCV particles and HCV-like particles (HCV-LP) suitable for a qualitative single-cycle entry assay, completely independent of HCV replication. To adapt this system as a single assay to study HCV-LP entry, HCV non-structural genes were replaced with a heterologous gene that upon viral-entry triggers firefly luciferase and EGFP expressions in target as well as non-permissive cells. The pretreatment of HCV-replication permissive HuH-7.5 cells with siRNA targeting HCV candidate receptors inhibited viral entry. These new systems enable production of authentic HCV infectious particles as well as HCV-LPs suitable for single-cycle entry assays adaptable to high throughput screening. CRADA Opportunity: The NIAID OTD is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a novel system for producing infectious HCV virions and developing a reporter system for studying HCV entry. Please contact Michael Piziali at 301-496-2644 for more information.

Increasing the Effectiveness of Cancer Treatment: T Cell Receptors Designed to Release Interleukin-12 Specifically at Cancer Sites

Tue, 23 Jun 2009 11:00:00 GMT
Many conventional chemotherapy drugs currently utilized to treat cancer also yield harsh side effects in patients. In addition, many patients do not respond to generalized chemotherapy and radiation treatments for cancer. There is an urgent need to develop new therapeutic strategies combining fewer side-effects and more specific anti-tumor activity in individual patients. Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual's innate and adaptive immune system to fight against specific diseases, including cancer.

T cell receptors (TCRs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit recognition signals by interacting with other proteins. When a TCR is stimulated by an antigen, such as a tumor antigen, some signaling pathways activated in the cell lead to the production of cytokines, which mediate the immune response.

Scientists at the National Institutes of Health (NIH) have developed T cells genetically engineered to express the human interleukin 12 (IL-12) cytokine only in the tumor environment. Specifically, these T cells have been designed to express a human IL-12 gene under the control of the nuclear factor of activated T cells (NFAT) promoter. When the TCR on these T cells recognizes a tumor antigen, IL-12 expression is induced through activation of the NFAT promoter. Thus, IL-12 is only released at the cancer site and only after the activation of the T cell. This technology makes it possible to control the expression of IL-12 to enhance T cell cytolytic activity while also reducing or eliminating the IL-12 toxicity observed with other IL-12 related therapies. Infusing these IL-12 expressing T cells into patients via adoptive immunotherapy could prove to be powerful new tools for attacking tumors. CRADA Opportunity: The National Cancer Institute, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize adoptive immunotherapies or the development of cancer therapeutics based on the use of T cell receptors. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Use of MMP-8 as a Prognostic Marker for Melanoma

Mon, 08 Jun 2009 15:00:00 GMT
Cutaneous malignant melanoma is the most common fatal skin cancer, and the incidence of this disease increases each year. The average survival time for patients diagnosed with malignant melanoma is less than ten months. Consequently, it is important to identify and understand genetic alterations leading to malignant melanoma so that new treatments strategies can be developed.

Matrix Metalloproteinases (MMPs) have been associated with increased metastasis and several small molecule inhibitors have been developed as potential anticancer agents. Unfortunately, these inhibitors have been largely unsuccessful despite the research suggesting otherwise and it is clear that additional analyses are warranted. The NIH inventors have recently performed a mutational analysis of the MMP gene family in human cutaneous metastatic melanoma and have identified several novel somatic mutations, most notably mutations in MMP-8. This invention provides methods of identifying specific inhibitors to MMP-8 that could be used to treat patients with MMP-8 mutations. It also provides methods for predicting the prognosis of patients with MMP-8 mutations. Thus, this invention could not only help identify the roles of specific MMPs in melanoma, but also help further the development MMP inhibitors to treat melanoma patients. CRADA Opportunity: The National Human Genome Research Institute’s Cancer Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, and/or commercialize this newly identified candidate melanoma diagnostic and prognostic marker as well as to identify and develop possible MMP-8 activators for testing as possible anti-melanoma agents. Please contact NHGRI’s Technology Development Coordinator (TDC) Claire T. Driscoll at cdriscol@mail.nih.gov for more information.

Mouse Model of Individual Unresponsive to Interferon

Mon, 08 Jun 2009 19:00:00 GMT
NIAID has developed a mouse model that produces very high levels of Interferon-alpha-receptor 2 (IFNAR2), both in liver cells and free-floating in serum.

Chronic co-infection of HIV and hepatitis C virus (HCV) is associated with increased overall morbidity and mortality compared to those infected with just one virus. Recent data further suggests that co-infection is also associated with a more rapid progression of liver disease, higher HCV RNA viral levels, decreased cure rate of HCV, and increased toxicities of anti-HCV therapy. Finally, clinical trials have shown that many patients infected with both viruses do not respond to Interferon-based therapy. Research strongly suggests that non-responding patients have an increased level of a free-floating form of IFNAR2, which could block Interferon activity.

Resistance to Interferon therapy also occurs in other diseases, such as autoimmune diseases (e.g., lupus, scleroderma, psoriasis, vasculitis) and certain forms of cancer (e.g., Kaposi’s sarcoma, follicular lymphoma). The various means by which resistance arises is currently being researched. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, is interested in collaborative research directed toward molecular strategies for vaccine and antiviral development, and animal models of viral hepatitis C. Please contact William Ronnenberg at 301-451-3522 or wronnenberg@niaid.nih.gov for more information.

Improved Antibodies Against ErbB4/Her4

Mon, 08 Jun 2009 23:00:00 GMT
ErbB4/Her4 is a receptor tyrosine kinase that regulates cell proliferation, cell differentiation and cell survival. ErbB4 has been implicated in the pathology of numerous cancers (e.g., breast cancer, non-small cell lung carcinoma, adenocarcinoma), as well as psychiatric disorders (e.g., schizophrenia). As a result, ErbB4 is an excellent target for developing therapies against these diseases. Unfortunately, the study of ErbB4 has been slowed by the lack of highly specific and functional antibodies against the receptor.

In order to overcome the deficiencies with current ErbB4 antibodies, NIH inventors have generated three rabbit monoclonal antibodies with improved properties and versatility. Specifically, the mAb-6, mAb-7 and mAb-10 hybridomas produce antibodies with a high degree of specificity and affinity for ErbB4. These antibodies recognize specific epitopes on the intracellular domains of ErbB4 without cross-reaction against other proteins, and can be used successfully in the immunostaining of fixed tissue. Each antibody recognizes both human and mouse ErbB4, whereas only mAb-7 and mAb-10 recognize rat ErbB4. CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Neurobiology, is seeking statements of capability or interest from parties interested in collaborative research to further evaluate or commercialize specific rabbit monoclonal antibodies generated against the ErbB4 receptor (also known as HER4). Please contact Joseph Conrad III, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information.

Self-Expanding Stent for Valve Replacement

Tue, 02 Jun 2009 03:00:00 GMT
Aortic stenosis and aortic regurgitation are the most common types of aortic valvular diseases. Such diseased aortic valves in the body are traditionally replaced with valve prosthesis by an open surgical implantation. Available for licensing and commercial development is intellectual property covering stents for use with valve prostheses. As illustrated below, one possible embodiment of the invention includes a self-expandable stent with an elastic tubular latticework having radial and longitudinal direction. The stent geometry and mechanical parameters provide more anatomically-correct placement and the flexible scaffolding of the valve (using an interconnected four-sided polygons and longitudinal rods comprising a self-expanding stent with a plurality of struts connecting a plurality of rods) allow for secure implantation with adaptable apposition of the prosthesis in the aorta.

CRADA Opportunity: The National Heart, Lung, and Blood Institute, Cardiothoracic Surgery Research Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Peg Koelbe at 301-594-4095 or koelblep@nhlbi.nih.gov for more information.

New Weapons to Attack Cancer: T Cell Receptors Designed to Recognize Tumors with Enhanced Affinity

Thu, 28 May 2009 07:00:00 GMT
Given the unpleasant side-effects associated with many cancer drugs, there is an urgent need to develop new therapeutic strategies combining fewer side-effects and more specific anti-tumor activity. Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual's innate and adaptive immune system to fight against specific diseases, including cancer.

T cell receptors (TCRs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit recognition signals by interacting with other proteins.

Scientists at the National Institutes of Health (NIH) have developed T cells with an enhanced ability to recognize the tumor associated antigens (TAAs) NY-ESO-1 and MART-1. These T cells were engineered to increase their ability to recognize these TAAs by making small genetic modifications to the TCRs that recognize these TAAs. NY-ESO-1 is a cancer-testis antigen found in normal testis and various tumors. MART-1 is a melanoma antigen found on normal melanocytes and overexpressed in malignant melanomas. Previous versions of gene-modified T cells developed by these researchers to attack tumors demonstrated objective clinical responses in some cancer patients, which validated gene-modified T cell adoptive immunotherapy as a promising cancer treatment strategy. These latest versions of the NY-ESO-1 and MART-1 specific TCRs, designated 1G4 NY-ESO-1 and DMF5 MART-1, were rationally engineered to enhance anti-tumor activity. These TCRs cause T cells to exhibit enhanced cytokine production and increased lysis of tumor cells when stimulated with NY-ESO-1 or MART-1. Infusing these T cells into patients via adoptive immunotherapy could prove to be powerful new tools for attacking tumors. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize TCRs that enhance the function of gene-modified T cells. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

T Cells Attacking Cancer: T Cell Receptors that Recognize the Tyrosinase Tumor Antigen

Thu, 28 May 2009 11:00:00 GMT
A problem with current chemotherapy-based cancer treatments is the harsh side-effects associated with many cancer drugs. Thus, there is an urgent need to develop new therapeutic strategies combining fewer side-effects and more specific anti-tumor activity. Adoptive cell transfer (ACT) is a promising new immunotherapeutic approach to treat cancer and other diseases by directing an individual's innate and adaptive immune system to recognize specific disease-associated antigens.

T cell receptors (TCRs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit recognition signals by interacting with other proteins.

Scientists at the National Institutes of Health (NIH) have isolated T cells that recognize the human tyrosinase tumor-associated antigen (TAA) from the tumor infiltrating lymphocytes (TIL) of a melanoma cancer patient. The human tyrosinase antigen is a tumor antigen expressed in a variety of cancers, including skin cancer (melanoma) and brain cancer (glioblastoma). Utilizing the tyrosinase specific T cells, these scientists developed human/mouse hybrid TCRs with enhanced affinity for the tyrosinase TAA. The TCR sequences were modified by making specific amino acid substitutions and replacing certain TCR regions with mouse homologues. These TCRs also showed CD8-independency and, thus, can be expressed in both CD8 and CD4 T cells. T cells expressing these engineered TCRs recognize skin and brain tumor cells in culture. These T cells also exhibit enhanced cytokine induction and better tumor reactivity compared to unmodified TCRs. Previous versions of gene-modified T cells developed by NIH researchers demonstrated objective clinical responses in some cancer patients, which have validated gene-modified T cell immunotherapy as a promising cancer treatment strategy. TCRs directed against the tyrosinase TAA could serve as valuable new immunotherapeutic tools for attacking tumors, especially in patients whose tumors do not express other common TAAs. CRADA Opportunity: The National Cancer Institute, Surgery Branch, Tumor Immunology Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize T Cells Attacking Cancer: T Cell Receptors that Recognize the Tyrosinase Tumor Antigen. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Diagnostic Markers for Melanoma

Thu, 28 May 2009 15:00:00 GMT
This invention relates to diagnostic and prognostic markers for melanoma. It discloses the identification of somatic mutations in genes of the microphthalmia-associated transcription factor (MITF) pathway in patients with melanoma.

Melanoma is an aggressive and often fatal cancer with increasing incidence worldwide. Previous studies have linked the MITF pathway to the progression of melanoma. However, little is known about somatic mutations in genes of the MITF pathway that contribute to the development and progression of melanoma. To assess the role of the MITF pathway in melanoma, NIH investigators evaluated primary and metastatic melanoma samples for the presence of somatic mutations in two genes of the MITF pathway, MITF and SRY (sex determining region Y)-box 10 (SOX10). They identified 16 previously unidentified somatic mutations in these genes. These studies suggest that MITF and SOX10 genes be used as diagnostic markers in human metastatic melanoma. CRADA Opportunity: The National Human Genome Research Institute's Cancer Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these newly identified candidate melanoma diagnostic and prognostic markers. Please contact NHGRI's Technology Development Coordinator (TDC) Claire T. Driscoll at cdriscol@mail.nih.gov for more information.

Method for the Diagnosis and Prognosis of Age-Related Cardiovascular Disorders

Thu, 28 May 2009 19:00:00 GMT
NIH investigators have discovered a method for the diagnosis and prognosis of cardiovascular aging. Current methodologies include the measurement of patient lipid profiles or expression of up to two proteins. In contrast, this technology utilizes the expression levels of a panel of proteins not previously known to be related to cardiovascular aging and may prove to be a more accurate diagnostic or prognostic of cardiovascular aging than currently available tests or it may improve the accuracy of currently available tests when used in concert.

The technology relates to methods for determining susceptibility to having an extremely common age-associated vascular disorder. It also describes the subsequent use of these proteins as markers for disease. While the underlying cellular and molecular mechanisms of age-related vascular disease remain largely undefined, the expression levels of the genes described in this technology have been empirically determined to differ between healthy and age-inflamed arterial tissue. Further, this technology includes a companion mass spectroscopic-based methodology for reproducible quantification of specific expression levels of interest. CRADA Opportunity: The National Institute on Aging, Cardiovascular Biology Unit-Vascular Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize idea of how to assess and retard accelerated arterial aging and its attendant risks for atherosclerosis and hypertension. Please contact Vio Conley at 301-496-0477 or conleyv@mail.nih.gov for more information.

Methods for Identifying Breast Cancer Patients for Therapy with mTOR Inhibitors

Thu, 28 May 2009 23:00:00 GMT
This technology relates to methods of identifying individuals with invasive breast cancer who may benefit from treatment with an inhibitor of mammalian Target of Rapamycin (mTOR), particularly those having a gene amplification including chromosome 8p11-12 or a portion thereof. Chromosome 8p11-12 is the second most commonly amplified region in breast cancer cases, after HER2 amplification at chromosome 17. Similar to HER2 amplification, the amplification of 8p11-12 is associated with decreased survival. However, whereas patients diagnosed with HER2 amplifications can be more effectively treated with adjuvant therapy using HER2 inhibitors such as trastuzumab, no specific therapy has been identified for breast cancer patients having an amplification of chromosome 8p11-12.

Investigators at NIH have shown that amplification of chromosome 8p11-12 leads to increased copy number of the gene for eukaryotic translation initiation factor 4E binding protein 1, or EIF4EBP1 and elevated expression of the protein in these breast cancer cell lines. EIF4E is a rate limiting component of a multi-subunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. EIF4EBP1 interacts and inhibits EIF4E complex assembly and thus, represses translation. In breast cancer cell lines with EIF4EBP1 amplification, the elevated EIF4EBP1 is largely inactivated via hyperphosphorylation. As the phosphorylation of EIF4EBP1 is controlled by mTOR, its hyperphosphorylation can be reversed with rapamycin. Indeed, rapamycin is much more effective in inhibiting the formation of active translational complex and the growth of breast cancer cells with chromosome 8p11-12/EIF4EBP1 amplification. Thus, detection of chromosome 8p11-12 amplification, and/or over-expression or increased phosphorylation of EIF4EBP1 can be used to identify breast cancer patients for treatment with inhibitors of mTOR, such as rapamycin or its derivatives or analogs. CRADA Opportunity: The Genetics Branch at National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Inhibitors of CD25 to Treat Autoimmune Diseases and Tumors

Fri, 29 May 2009 03:00:00 GMT
This invention discloses therapeutics for the treatment of Multiple Sclerosis, uveitis, and certain cancers by providing methods and compositions for selectively blocking CD25 on T cells or dendritic cells. The therapeutics developed using the current technologies have the potential to exhibit superior specificity and minimal side-effects. In this invention, NIH investigators, for the first time, demonstrate that mature dendritic cells (mDC) use CD25 for trans-presentation of IL-2, and the blockade of CD25 on the surface of mDCs abrogates T cell proliferation. Further, CD25 expression on T cells is not only dispensable for their proliferation, but it also limits effector T cell survival. These observations form the basis for the development of novel therapies for certain cancers and autoimmune disorders. CRADA Opportunity: The National Institute of Neurological Disorders and Stoke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of treating multiple sclerosis by administering agents that block the interaction of dendritic cells and T cells via CD25. Please contact Dr. Martha Lubet at 301-435-3120 or lubetm@mail.nih.gov for more information.

Broadly Applicable Modules for Improved Expression and Detection of Membrane Proteins

Thu, 28 May 2009 07:00:00 GMT
NIH investigators have designed and tested a set of expression modules that are applicable to a wide variety of membrane proteins. Prior to this invention, cloned membrane proteins have sometimes been difficult to detect due to the lack of effective antibodies. Moreover, currently available expression vectors lack the signal sequences, tags, and multiple cloning sites to clone membrane proteins and express them on the cell surface. This invention is the first of its kind to contain all of these elements to facilitate biochemical studies on membrane proteins.

This technology is a set of nucleic acid modules designed for the expression and tagging of membrane proteins in mammalian cells. The module includes a signal peptide, an exchangeable tag, and a multiple cloning site. The gene of a membrane protein may be conveniently inserted into the multiple cloning site, and the signal peptide will target the cloned membrane protein to the cell surface. The tag, in frame with the signal peptide, is either a fluorescent protein or an epitope for a known antibody, both of which enable detection of the protein by several standard biochemical methodologies. CRADA Opportunity: The National Institute on Aging, Laboratory of Cardiovascular Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the technology of mammalian membrane protein expression and detection. Please contact Vio Conley at 301-496-0477 or conleyv@mail.nih.gov for more information.

Immortalized Virus-Free Human Placental Cell Lines

Thu, 28 May 2009 11:00:00 GMT
This technology provides immortalized virus-free human placental cell lines. To develop these cell lines, human placental cells were immortalized with adenovirus-origin-minus (ori-)-simian virus-40 (SV40) recombinant viruses containing either wild-type or temperature-sensitive (ts) A mutants of SV40. Cells transformed with the SV40 tsA chimera (HP-A1 and HP-A2), but not the SV40 wild-type chimera (HP-W1), were conditional for transformation. All three cell lines expressed trophoblast-specific genes, including placental specific genes and the alpha- and beta-subunits of hCG.

These immortalized virus-free human placental cell lines expressing major proteins of human trophoblasts provide efficient in vitro models to study placental functions. CRADA Opportunity: The National Institute of Child Health and Human Development, Section on Cellular Differentiation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Immortalized Virus-Free Human Placental Cell Lines. Please contact Joseph Conrad III, Ph.D. at 301-435-3107 or jmconrad@mail.nih.gov for more information.

Novel Method of Treating Cancer Using Ixolaris

Thu, 28 May 2009 15:00:00 GMT
Aggressive tumors spread between tissues in a process known as metastasis. Tumor metastasis, particularly with regard to brain cancer (gliomas), has been linked to the aberrant expression of membrane-bound tissue factor (TF). TF normally functions as a blood coagulation factor and can lead to the production of pro-angiogenesis factors such as vascular endothelial growth factor (VEGF). By doing this in the vicinity of tumors, TF may enhance both tumor growth and the ability of tumors to metastasize.

Ixolaris is a protein that prevents the initiation of blood coagulation, specifically by inhibiting TF. NIH inventors have explored the possibility that Ixolaris could be effective as an anti-cancer therapy. As an inhibitor of TF, Ixolaris could potentially inhibit the function of TF, thereby reducing the ability of a tumor to develop and to metastasize. Recent data show that Ixolaris has the ability to prevent tumor growth in vivo using mouse xenograft models. Importantly, the inhibition in vivo occurred without noticeable bleeding. Since Ixolaris is not immunogenic, it might be an excellent candidate as an anti-cancer therapeutic. CRADA Opportunity: The NIAID, OTD, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Ixolaris for cancer treatment. Please contact Dana Hsu at 301-496-2644 for more information.

Identification of Renal Cell Carcinoma Biomarkers

Fri, 15 May 2009 19:00:00 GMT
This invention describes the identification of potential renal cancer biomarkers which could be utilized in the development of a renal cancer diagnostics. The invention identified cancer protein biomarkers from clinically relevant samples including peripheral blood and fresh frozen tissues. Vast availability of fresh frozen tissues and peripheral blood specimens that are easily obtained could lead to clinical tests amenable to therapeutic, prognostic and even early screening tests for renal cell carcinoma and other malignancies. CRADA Opportunity: The National Cancer Institute Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Simple Biosensors Based on Electrical Percolation Biological Semiconductors

Fri, 15 May 2009 23:00:00 GMT
The invention offered for licensing is in the field of biosensors with application in diagnostics and in regulation of implantable biomedical devices. More specifically, it is related to biological semiconductors based on the electrical percolation of single-walled carbon nanotubes (SWNTs). The nanotubes are embedded with biological ligands (e.g., antibodies). The electrical resistance of a semiconducting SWNT is found to dramatically increase upon the actuation by a specific antigen. Measurement of the change in resistance correlates with the concentration of the specific antigen and thus provides for quantitative determination and diagnostics of biological samples. The simple printing fabrication of electrical percolation biological semiconductors (EPBSC) can facilitate assembly of numerous types of gates (e.g., antibodies, DNA, etc.) and print many of such gates on the same chip for the creation of biological CPUs for various biomedical applications, including direct biodetection and regulation of implantable biomedical devices. CRADA Opportunity: The National Cancer Institute, Cancer Diagnostic Program, and the Food and Drug Administration, the Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Electrical Percolation Biological Semiconductors for biodetection. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Mobilizing the Body to Fight Cancer: T Cell Receptors Specific for the Tumor Antigen Survivin

Sat, 16 May 2009 03:00:00 GMT
A major drawback of current chemotherapy-based cancer treatments is the harsh side-effects associated with many cancer drugs. Thus, there is an urgent need to develop new therapeutic strategies combining fewer side-effects and more specific anti-tumor activity. Immunotherapy is a promising new cancer therapeutic approach that directs an individual's innate and adaptive immune system to fight against specific diseases, including cancer.

T cell receptors (TCRs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit recognition signals by interacting with other proteins.

Scientists at the National Institutes of Health (NIH) have developed genetically-modified T cells, which possess TCRs that specifically recognize human survivin, a tumor antigen expressed in many adult and pediatric cancers that is absent from most normal tissues. Non-human T cells that recognized human survivin peptides with high affinity in the context of human leukocyte antigen (HLA) alleles were identified. Then, using recombinant DNA technology, the survivin-specific TCRs from the non-human T cells were fused to human TCR backbones and expressed in human T cells. The resulting survivin-specific human T cells could prove to be powerful new immunotherapeutic tools for attacking survivin-expressing tumors after infusion into patients. CRADA Opportunity: The National Cancer Institute Pediatric Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize genetically engineered lymphocytes with specificity for human survivin. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Salcut-NH2: A Novel Target for Development of Anti-Tumorigenic, Anti-Angiogenic Therapeutics and Diagnostics

Tue, 05 May 2009 07:00:00 GMT
Salcut-NH2, a novel amidated peptide derived from the Apelin proprotein, is shown to induce the proliferation of cells. Uncontrolled cell proliferation is the salient feature of cancer. Thus, therapeutics that stop this aberrant cell division are very desirable. Salcut-NH2 can be the basis for developing novel inhibitors of cancer growth such as modified peptide antagonists like salcut-glycine (salcut-Gly). Alternately, salcut-NH2 could be the target of antibody therapies that block its activity. In some instances, such as wound healing, inducing cell proliferation would be advantageous. It also has been demonstrated that salcut-NH2 induces angiogenesis so it may also have application as a topically administered therapeutic for speeding the healing of skin wounds. Finally, increasing levels of salcut-NH2 in body fluids may be reflective of disease progression. A diagnostic kit for salcut-NH2 could potentially be developed for the prognosis of a variety of diseases associated with aberrant cell proliferation or angiogenesis. CRADA Opportunity: The National Cancer Institute Angiogenesis Core Facility is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize 1) Identification of new biological functions for Salcut-NH2 or 2) Development of compounds that suppress or augment Salcut-NH2 bioactivity. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Immunogenic West Nile Virus-Like Particles

Tue, 05 May 2009 11:00:00 GMT
Currently, no specific vaccine or therapy for West Nile Virus (WNV) is available for human use; a killed-virus vaccine and booster is in use for horses (efficacy not yet reported). Virus-like particles (VLPs) are an exciting new strategy, as it combines the safety of killed-virus and DNA-based vaccines with the potential for immunogenicity of live-attenuated virus. VLPs have been used in approved vaccine for humans, including human papilloma virus (HPV). Generating VLPs for West Nile Virus, however, has proven difficult.

The inventors have successfully generated West Nile VLPs in insect cells by using recombinant baculoviruses expressing the WNV structural proteins prME or CprME. Mice immunized with purified West Nile VLPs developed antibodies specific to WNV with potent neutralizing activities; moreover, the mice showed no morbidity or mortality after a subsequent challenge with live WNV and showed no evidence of viremia or viral RNA in the spleen or brain.

The patent application covers applications ranging from pharmaceutical/vaccine preparations for WNV-LPs to methods for making and using them. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Liver Diseases Branch, is seeking parties interested in collaborative research directed toward molecular strategies for vaccine and antiviral development, and animal models of viral hepatitis C. For more information, please contact Dr. T. Jake Liang at 301-496-1721, jliang@nih.gov, or Ms. Patricia Lake at 301-594-6762, lakep@mail.nih.gov.

Method of Detecting and Quantifying Contaminants in Heparin Preparations

Tue, 05 May 2009 15:00:00 GMT
Heparin is a naturally occurring acidic carbohydrate produced commercially from extracts of animal tissues (such as bovine lung or porcine intestine) and is used in the treatment of a wide range of diseases in addition to their classic anticoagulant activity. Heparin is also used to coat many medical devices, such as catheters, syringes, stents and filters. Recently, certain lots of heparin were associated with serious side effects and adverse events. Recalls were issued in multiple countries and it became evident that there was an extensive problem with heparin manufacture.

Traditional tests may not be able to determine the presence of contaminant(s) without lyophilizing and concentrating each sample and may not be suitable for testing finished medical devices. Therefore, there is a demonstrated need to develop other assay methods for detecting contaminating oversulfated compounds of any source in heparin and heparin derived products.

This technology relates to methods for detecting and/or quantifying oversulfated glycosaminoglycans based on inhibition of nucleic acid polymerases and resistance to enzymatic degradation. It also relates to the use of these methods to screen and quantify pharmaceutical preparations such as heparin preparations for oversulfated contaminants. CRADA Opportunity: The FDA, Division of Therapeutic Proteins, Laboratory of Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this high throughput screening test for oversulfated glycosamineglycan contaminants in heparin. Please contact Daniela Verthelyi at daniela.verthelyi@fda.hhs.gov or Alice Welch at alice.welch@fda.hhs.gov for more information.

Novel Means of Regulation of Gene Expression: Modular and Artificial Splicing Factors

Tue, 05 May 2009 19:00:00 GMT
This discovery provides a new therapeutic approach for treatment of diseases caused by altered gene regulation resulting from defective alternative splicing of genes. This technology offers the following advantages over currently available methods for regulating splicing: a) delivery can be through standard gene therapy methods, such as viral vectors, b) site of delivery of the artificial splicing factors can be controlled, which enables targeted expression and limited side effects, and c) the artificial splicing factors described here can be readily adapted to a variety of splicing effector modules. This invention provides proteins that combine an RNA recognition module that can specifically target an endogenous pre-mRNA with splicing effector modules that alter splicing to favor a particular isoform of a mature mRNA.

The artificial splicing factors disclosed here can be used to treat conditions requiring directed alternative splicing. For example, the artificial splicing factors described here can be used in combination with other anti-tumor drugs as a cancer treatment. Other examples where this technology may find use include diabetes (insulin receptor), psoriasis (fibronectin), polycystic kidney disease (PKD2), and prostate cancer (fibroblast growth factor receptor 2). CRADA Opportunity: The NIEHS Division of Intramural Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Modular and Artificial Splicing Factors. Please contact Elizabeth M. Denholm, Ph.D. at 919-541-0981 or denholme@niehs.nih.gov or Traci Hall, Ph.D. at hall4@niehs.nih.gov for more information.

Mast Cells Defective in the Syk Protein Tyrosine Kinase

Tue, 05 May 2009 23:00:00 GMT
NIH investigators, through screening for variants of RBL-2H3 cells, have identified and developed TB1A2 mast cells that are defective in the expression of the Syk protein tyrosine kinase. These cells had no detectable Syk protein by immunoblotting or in vitro kinase reaction, and no detectable Syk mRNA by Northern hybridization. These TB1A2 cells failed to secrete or generate cytokines after high affinity receptor for immunoglobulin E (Fc epsilon RI) stimulation. In these Syk-deficient TB1A2 cells, aggregation of these receptors did not induce histamine release and there was no detectable increase in total cellular protein tyrosine phosphorylation. However, stimulation of these cells with the calcium ionophore did induce degranulation. These cells provide a useful experimental model to study the role of Syk tyrosine kinase in signal transduction pathways in immune cells. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Oral Infection and Immunity Branch, Receptors and Signal Transduction Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

Small Molecule Activators of Human Pyruvate Kinase for Treatment of Cancer and Enzyme-Deficient Hemolytic Anemia

Wed, 06 May 2009 03:00:00 GMT
NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.

The invention described here is a series of small molecules that activate pyruvate kinase (PK) isoform M2. PK-M2 is a critical metabolic enzyme that is affected in all forms of cancer. Inactivation of PK-M2 leads to a buildup of metabolic intermediates inside the cell. Tumor cells require a buildup of metabolic intermediates in order to undergo rapid cell growth and proliferation. Hence, activation of PK-M2 in tumor cells may prevent the buildup of metabolic intermediates and thereby stall tumor cell proliferation or destroy the tumor cells. Further, while in normal adult cells only PK isoforms R, L, or M1 are active, in all tumors only PK-M2 is active. Therefore, PK-M2 activation would affect only tumor cells, and small-molecule PK-M2 activators are not expected to be toxic to healthy cells.

In addition, in patients with PK-R deficiency the buildup of metabolic intermediates in red blood cells ultimately leads to the loss of water from the cells and cell death. Small-molecule induced activation of PK-R in PK-deficient red blood cells may enhance vitality of these cells and decrease or eliminate enzyme-deficient hemolytic anemia in a patient. CRADA Opportunity: The NIH Chemical Genomics Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize appropriate lead compounds described in U.S. Provisional Application No. 61/199,763. Please contact Dr. Craig J. Thomas via e-mail (craigt@nhgri.nih.gov) for more information.

Magnetic Resonance Specimen Evaluation Using Multiple Pulse Field Gradient Sequences

Mon, 04 May 2009 07:00:00 GMT
The invention proposes and claims an MRI-method that is based on the measurement and acquisition of multiple pulsed field gradient (m-PFG) rather than the previously used single-pulsed field gradient (s-PFG) MRI sequences. In particular, double PFG (d-PFG) sequences offer higher sensitivity and greater robustness, as it is more sensitive to the effect of “restriction”, i.e., to water trapped within the axon’s intracellular space, and thus to the diameter of the axons. It renders the MR sequence more sensitive to “pore size” and “pore shape” and thus makes the measurement of the ADD more sensitive and accurate. Moreover, measurements using the multiple-PFG sequence can be performed readily at “low b” or “low q”, making it biologically relevant and clinically feasible.

A detailed announcement describing the licensing opportunity for this and related technologies referenced below was published in the Federal Register on Tuesday, April 14, 2009 (74 FR 17199-17201). CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Tissue Biophysics and Biomimetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel MRI methods to probe tissue structure and organization, particularly for neuroimaging applications. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information.

Non-Invasive in vivo MRI Axon Diameter Measurement Methods

Mon, 04 May 2009 11:00:00 GMT
This invention describes an improvement and continuation of the CHARMED MRI framework described above, extending this technology to measure the axon diameter distribution (ADD) of nerve bundles (fascicles) in the central and peripheral nervous systems.

The invention essentially consists of a non-obvious combination of CHARMED MRI and an improvement of an NMR method, originally developed for particle sizing in porous media applications, which was extended and enhanced to provide a direct measurement of the ADD within nerve fascicles in the brain, spine or other parts of the peripheral nervous system on a voxel-by-voxel basis. Additionally this approach can be extended to measure the fiber orientation distribution of axons within each voxel of an imaging volume and particularly the myelin content within each voxel.

The significance of this invention is that it represents a way to provide a non-invasive, painless, in vivo measurement of microanatomical (histological) features of nerves (and possibly muscles) that are critically important in medicine and the neurosciences and previously were only available using invasive histological means requiring biopsy. The ADD is altered in abnormal development (possibly even in autism), in degenerative processes (e.g., aging, alcoholism, Alzheimer's disease) and diseases such as ALS (Lou Gehrig's disease). The ADD is a critically important parameter of a nerve bundle from a neuroscience perspective because axon diameter determines the conduction velocity of action potentials, and thus the arrival time and latency of nerve impulses traveling along them. The orientation or directional distribution of axons is important in Tractography applications to help determine how different cortical regions of the brain are connected to each other via white matter pathways. Myelin is dynamically regulated in vivo and affects the electrical insulating property of axons, and thus the conduction velocity of nerves. Myelin content is a critically important parameter in MS and a large number of dysmyelinating and demyelinating diseases as well as in normal and abnormal development.

A detailed announcement describing the licensing opportunity for this and related technologies referenced below was published in the Federal Register on Tuesday, April 14, 2009 (74 FR 17199-17201). CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Tissue Biophysics and Biomimetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel MRI methods to probe tissue structure and organization, particularly for neuroimaging applications. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information.

Identification of Subjects Likely to Benefit from Copper Treatment

Mon, 04 May 2009 15:00:00 GMT
Menkes disease is an infantile onset X-linked recessive neurodegenerative disorder caused by deficiency or dysfunction of a copper-transporting ATPase, ATP7A. The clinical and pathologic features of this condition reflect decreased activities of enzymes that require copper as a cofactor, including dopamine-beta-hydrolase, cytochrome c oxidase and lysyl oxidase. Recent studies indicate that ATP7A normally responds to N-methyl-D-aspartate receptor activation in the brain, and an impaired response probably contributes to the neuropathology of Menkes disease. Affected infants appear healthy at birth and develop normally for 6 to 8 weeks. Subsequently, hypotonia, seizures and failure to thrive occur and death by 3 years of age is typical. Occipital horn syndrome (OHS) is also caused by mutations in the copper transporting ATPase ATP7A, although its symptoms are milder than Menkes syndrome, including occipital horns and lax skin and joints.

Treatment with daily copper injections may improve the outcome in Menkes disease if commenced within days after birth; however, newborn screening for this disorder is not available and early detection is difficult because clinical abnormalities in affected newborns are absent or subtle. Moreover, the usual biochemical markers (low serum copper and ceruloplasmin) are unreliable predictors in the neonatal period, since levels in healthy newborns are low and overlap with those in infants with Menkes disease. Although molecular diagnosis is available, its use is complicated by the diversity of mutation types and the large size of ATP7A (about 140kb). Thus, there is a need for improved methods for early detection of infants with Menkes disease or OHS in order to improve outcomes.

This technology relates to methods of identifying individuals who may benefit from treatment with copper, particularly those having Menkes disease or Occipital Horn Syndrome. CRADA Opportunity: The National Institute of Child Health and Human Development, Division of Intramural Research, Molecular Medicine Program, Unit on Pediatric Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize population-based newborn screening for Menkes disease and related disorders of copper transport in order to identify subjects likely to benefit from copper injections and other treatments. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information.

An Imaging Radiotracer for the Noninvasive Detection of HER2-positive Tumors

Mon, 04 May 2009 19:00:00 GMT
Investigators at the NIH have developed a novel imaging radiotracer composed of an Affibody® molecule uniquely labeled with ¹⁸F for noninvasively locating and measuring the expression of HER2 breast cancer biomarker in tumors anywhere in the body. The over expression of HER2 in cells is a diagnostic marker for a particularly aggressive form of breast cancer. Currently, localized biopsies are needed to diagnose HER2-positive breast cancer. Noninvasive detection of HER2-positive cells in whole body will help to identify patients that can benefit from HER2-targeted therapies such as the monoclonal antibody trastuzumab. This imaging compound will also be useful for monitoring the tumor response to HER2-targeted therapies. The use of an Affibody® molecule is advantageous because it is a recombinant protein of relatively small size (more than 20 times smaller than antibodies), readily producible and has a high binding affinity for HER2. This allows the imaging compound to permeate the body easily and bind to the HER2-positive cells selectively. Conjugating the Affibody® molecule to the positron-emitting radionuclide ¹⁸F enables noninvasive imaging using positron emission tomography (PET). The utility of this targeted radiotracer for detecting HER2-positive tumors has already been validated in animals. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Radiation Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Affibody® molecules for diagnosis and molecular therapy of HER1- or HER2-positive tumors. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Peptides for Treating Mesothelin- and/or CA125-Expressing Cancers

Mon, 04 May 2009 23:00:00 GMT
Mesothelin is a cell surface glycoprotein that is highly expressed in many cancers, including malignant mesothelioma and ovarian cancer. Mesothelin interacts with another cell surface protein that is also highly expressed on some cancer cells: CA125 (MUC16). Evidence indicates that this interaction mediates cell adhesion during tumor implantation and metastasis. This suggested that the disruption of the mesothelin-CA125 interaction may prevent the growth and spreading of tumors.

NIH inventors have generated specific peptides, based on the CA125 binding domain of mesothelin, that block the interaction between mesothelin and CA125. Significantly, blocking the interaction disrupted cell adhesion in cancer cells expressing both mesothelin and CA125. Antibodies that recognize the specific mesothelin peptides were also capable of disrupting the mesothelin-CA125 interaction. The peptides bound CA125 on cancer cells. As a result, these peptides are excellent candidates for a new cancer therapeutic. CRADA Opportunity: The National Cancer Institute, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize peptides for treating mesothelin- and/or CA125-expressing cancers. Please contact Mitchell Ho at 301-451-8727 and/or homi@mail.nih.gov for more information.

Treating Cancer through Immunotherapy with Herceptin-Based Receptors Specific for ErbB2 (Her2/Neu)

Tue, 05 May 2009 03:00:00 GMT
There is an urgent need to develop new therapeutic strategies for patients with cancer that combine fewer side-effects and more specific anti-tumor activity. Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual’s innate and adaptive immune system to fight against specific diseases, including cancer.

Chimeric antigen receptors (CARs) are hybrid proteins consisting of the portion of an antibody that recognizes a tumor-associated antigen (TAA) fused to protein domains that signal to activate the CAR-expressing cell. Human cells that express CARs, most notably T cells, can recognize specific tumor antigens with high reactivity to mediate an immune response that promotes tumor killing in targeted cancer cells.

Scientists at the National Institutes of Health (NIH) have developed CARs with high affinity for the ErbB2 (also known as Her2/Neu) antigen, which is overexpressed on a variety of cancer cells, including lung, breast, colorectal, ovary, prostate, and head and neck squamous cell cancer. These ErbB2-specific CARs are herceptin-based receptors composed of the part of a humanized herceptin antibody that recognizes ErbB2 and a portion of the T cell receptor (TCR)-related protein, CD3. The herceptin-CAR framework was selected since the herceptin monoclonal antibody has been proven to be an effective treatment for breast cancer. These ErbB2-specific CARs expressed in the context of T cells could prove to be powerful new immunotherapeutic tools for attacking ErbB2+ tumors after their infusion into patients. CRADA Opportunity: Dr. Steven A. Rosenberg of the NCI Surgery Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutic T cell receptor technologies. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Live-Attenuated West Nile Virus Vaccines with Improved Immune Responses

Mon, 04 May 2009 07:00:00 GMT
West Nile virus (WNV), the etiologic agent of West Nile virus fever and encephalitis, is an emerging human and veterinary pathogen in North America. WNV also periodically poses a serious threat to public health in Africa, Australia, Europe, the Middle East, and Asia. There is no vaccine available. WNV strains are phylogenetically grouped into two distinct lineages based primarily on differences within the envelope (Env) protein gene segment. The highly virulent strains recently emergent on the North American continent are of lineage I. Lineage I viruses are primarily also isolated in the Middle East, Europe, and parts of Africa. Lineage II viruses are mostly isolated in Africa. Both lineages include highly neurovirulent as well as relatively attenuated strains of WNV.

WN vaccine viruses developed by others are chimeric live attenuated WN vaccine viruses. The genomes of these viruses encode the C and NS proteins of dengue or yellow fever virus, respectively, along with the WNV prM and Env proteins, which are the major targets of the humoral immune response to flaviviruses. These chimeric live attenuated WN vaccines have been successful in animal testing and some are currently in clinical trials. However, these vaccines have two potential disadvantages due to their heterogeneous genetic composition: (i) animal host range may be different from that of wild-type WNV, rendering the vaccines less than optimal for immunization of some at-risk species and (ii) the elicited immune response may be suboptimal in duration or quality, due to the absence from these vaccines of homologous WN NS proteins.

FDA’s technology that is available for licensing comprises live attenuated West Nile viruses that are not chimeric, but instead have one or more mutations in the 3' terminal stem loop secondary structure, resulting in decreased neurovirulence. The related patent application also claims methods of making the viruses claimed in the application and methods for using these viruses to prevent or treat WN infection. More specifically, the inventors modified infectious WN DNA such that all or segments of the wild-type WN 3' stem loop nucleotide sequence was replaced with analogous dengue virus serotype 2 3' stem loop sequences. The inventors also created a number of point mutations in the nucleotide sequence of the WN 3' stem loop sequence. CRADA Opportunity: The FDA Office of Vaccines Research & Review is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize West Nile Virus vaccines. Please contact Alice Y. Welch, Ph.D., at 301-827-0359 or Alice.Welch@fda.hhs.gov for more information.

Anti-Cancer Oligodeoxynucleotides

Mon, 04 May 2009 11:00:00 GMT
A majority of human cancers originate from epithelial tissue. A common cancer of epithelial cell origin is non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with more than seven hundred thousand (700,000) new cases diagnosed each year in the United States alone. BCC is rarely life-threatening because it is slow growing and is mostly localized. Unlike BCC, SCC metastasizes at a rate of two (2) to six (6) percent over several years after the initial diagnosis. A highly malignant form invades and destroys tissue, and then metastasizes, initially to a regional lymph node before more distant organs such as the lungs or brain are affected. SCC is commonly encountered in a number of epithelial tissues, including the oral cavity, esophagus, larynx, bronchi, intestines, colon, genital tract, and skin.

This application relates to suppressive CpG oligodeoxynucleotides (ODNs). This application claims suppressive ODN compositions and their use to prevent or delay the formation of a tumor, reducing the risk of developing a tumor, treating a tumor, preventing conversion of a benign to a malignant lesion, or preventing metastasis. Topical application of the ODNs of this invention in preclinical studies resulted in significantly fewer animals developing papillomas and fewer papillomas/animal. The invention also relates to use of suppressive ODNs to prevent/delay cancer when administered systemically as well as locally. CRADA Opportunity: The National Cancer Institute, Laboratory of Experimental Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Insect Salivary Proteins as Potent Adjuvants for Enhancing Immune Responses

Mon, 04 May 2009 15:00:00 GMT
This invention relates to the discovery that specific sand fly salivary proteins have marked effects on the outcome of Leishmania infection. These proteins have the ability to stimulate strong Th1 and Th2 responses. The Th1 responses with one protein, PpSP15, result in immune protection while the Th2 responses to another protein, PpSP44, exacerbate infection. The protective protein enhanced a specific immune response to the infection, suggesting that it acts as an adjuvant to alter the environment and presentation of the parasite antigens.

These immunogenic salivary proteins, capable of driving Th1 or Th2 responses, can be used as adjuvants in vaccine development for a broad spectrum of diseases that require different immune responses. They may therefore be used to enhance immune responses to pathogens other than Leishmania parasites. They are also very potent in their effect, and small doses are sufficient to elicit a strong immune response. This potency can reduce the need to use chemical adjuvants, which often require large mounts of material and can have deleterious side effects. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the Insect Salivary Proteins as potent immune response adjuvants. Please contact Charles Rainwater at crainwater@niaid.nih.gov or 301.496.2644 for more information.

Substituted Triazine and Purine Compounds for the Treatment of Chagas Disease and African Trypanosomiasis

Mon, 04 May 2009 19:00:00 GMT
Parasitic protozoa are responsible for a wide variety of infections in both humans and animals. Trypanosomiasis poses health risks to millions of people across multiple countries in Africa and North and South America. Visitors to these regions, such as business travelers and tourists, are also at risk for contracting parasitic diseases. There are two types of African trypanosomiasis, also known as sleeping sickness. One type is caused by the parasite Trypanosoma brucei gambiense, and the other is caused by the parasite Trypanosoma brucei rhodesiensi. If left untreated, African sleeping sickness results in death. Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects millions of people in Mexico and South and Central America. Untreated, Chagas disease causes decreased life expectancy and can also result in death.

The subject invention covers novel triazine and purine compounds that are inhibitors of key proteases (cruzain and Rhodesian) of the parasites Trypanosoma brucei rhodesiensi and Trypanosoma cruzi, respectively. CRADA Opportunity: The NIH Chemical Genomics Center (NCGC) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize appropriate lead compounds described in the patent application. Please contact Dr. Craig J. Thomas (craigt@nhgri.nih.gov) or Lili M. Portilla, MPA (Lilip@nih.gov) for more information.

Small-Molecule TSH Receptor Modulators for Diagnosis and Treatment of Thyroid Disease and Cancer

Mon, 04 May 2009 23:00:00 GMT
NIH investigators have discovered a series of low molecular weight thyroid-stimulating hormone (TSH) receptor modulators for use in evaluation and treatment of thyroid diseases, including thyroid cancer, hypothyroidism, and hyperthyroidism. Certain compounds encompassed by this technology are more potent and/or more specific TSH receptor activators than currently-available compounds; also, as small molecules, these compounds are orally available and are expected to be less costly and more straightforward to produce than recombinant protein counterparts currently on the market.

According to the National Cancer Institute, over 37,000 new cases of thyroid cancer were diagnosed in the United States in 2008, and over 1,500 people died of this disease. These numbers reflect a progressive increase in the incidence of thyroid cancer over the last several years. Because most cases of thyroid cancer are diagnosed in patients between the ages of 20 and 54, these patients will undergo decades of follow-up monitoring after cancer treatment. For the last decade, recombinant TSH protein has been used in this follow-up to increase detection sensitivity for recurrent or metastatic thyroid cancer, and to eliminate side effects associated with withdrawal of hormone replacement therapy. A small-molecule TSH receptor agonist encompassed by this technology would have utility similar to recombinant TSH, but would have several distinct advantages. For example, as a small molecule, rather than a recombinant protein, such a compound would be orally available, and would be less difficult and expensive to produce. These compounds are also more potent and/or specific for the TSH receptor than other known small-molecule TSH receptor agonists. In addition to use in thyroid cancer screening, these compounds may also be useful for adjunctive treatment (with radioactive iodide) of thyroid cancer, and certain forms of hypothyroidism.

Hyperthyroidism, or an overactive thyroid gland, affects about 1% of people in the United States and is often caused by autoimmune over-stimulation of the thyroid gland (Graves’ disease), or by thyroid tumors. Drugs currently used for treatment of hyperthyroidism inhibit synthesis of thyroid hormones; the TSH receptor antagonist compounds encompassed by this technology have the advantage of directly inhibiting activity of the TSH receptor, rather than inhibiting thyroid hormone synthesis. CRADA Opportunity: The NIDDK Clinical Endocrinology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize small molecule TSH receptor modulators. Please contact Marguerite J. Miller at 301-496-9003 or millermarg@mail.nih.gov for more information.

Modulating Expression of the Metastasis Suppressor MxA

Tue, 05 May 2009 03:00:00 GMT
The invention discloses compounds that could be used to inhibit metastases. The compounds of the current invention were discovered by high-throughput screening of a novel cell line engineered with a MxA reporter. The compounds could be used to treat metastatic cancers including prostate and melanomas by increasing MxA expression.

MxA expression reduces cell motility and metastases in a mouse model. Cells expressing MxA produced smaller tumors in engrafted mice compared to controls. When injected into mouse spleens, cells expressing MxA showed a significantly delayed metastasis, and the mice survived significantly longer than controls. Expression of MxA reduced cellular motility of prostate cancer cell lines in vitro and reduced cellular motility and invasiveness of the highly metastatic melanoma cell line LOX. In addition to the use of the instant MxA compounds as antimetastatic agents, MxA is a known effective anti-viral agent and the MxA-inducing compounds could be used to treat infections sensitive to the antiviral activity of MxA, which potentially include myxovirus-associated disease. CRADA Opportunity: The National Cancer Institute, Medical Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

On-Demand In Vitro Assembly of Protein Microarrays

Mon, 04 May 2009 07:00:00 GMT
Protein microarrays are becoming an indispensable biomedical tool to facilitate rapid high-throughput detection of protein-protein, protein-drug and protein-DNA interactions for large groups of proteins. The novel Protein Microarray of this invention is essentially a DNA microarray that becomes a protein microarray on demand and provides an efficient systematic approach to the study of protein interactions and drug target identification and validation, thereby speeding up the discovery process. The technology allows a large number of proteins to be synthesized and immobilized at their individual site of expression on an ordered array without the need for protein purification. As a result, proteins are ready for subsequent use in binding studies and other analysis.

The Protein Microarray is based on high affinity and high specificity of the protein-nucleic acid interaction of the Tus protein and the Ter site of E. coli. The DNA templates are arrayed on the microarray to perform dual function: (1) synthesizing the protein in situ (cell-free protein synthesis) in the array and (2) at the same time capturing the protein it synthesizes by DNA-protein interaction. This method utilizes an expression vector containing a DNA sequence which serves a dual purpose: (a) encoding proteins of interest fused to the Tus protein for in vitro synthesis of the protein and (b) encoding the Ter sequence, which captures the fusion protein through the high affinity interaction with the Tus protein. CRADA Opportunity: The National Cancer Institute Protein Expression Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize in vitro assembly of protein microarrays. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Transgenic Mice in which the Gene for MCP-1 is Deleted

Mon, 04 May 2009 11:00:00 GMT
Dr. Yoshimura has developed a transgenic mouse which does not express the chemokine MCP-1 due to a deletion of the gene for MCP-1. MCP-1 is a CC chemokine which is responsible for recruiting monocytes into sites of inflammation and cancer. Using a thioglycollate challenge as a measure of the impact of the deletion of MCP-1, MCP-1 deficient mice exhibit a 60% reduction in the number of monocytes/macrophages at 96 hours compared to wild type mice. Unlike previously generated MCP-1 deficient mice in which the expression of the neighboring gene for MCP-3 is down-regulated (our own data), the expression of MCP-3 is up-regulated in this mouse model. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize agents useful to treat patients with inflammation or cancer. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Diffusion Tensor and q-Space MRI Specimen Characterization

Mon, 04 May 2009 15:00:00 GMT
Diffusion Tensor MRI (DTI or DT-MRI) – a technique described in U.S. Patent 5,539,310 and implemented by all major commercial MRI systems – provides information primarily about how water diffuses in the extracellular compartment of tissues, where water mobility is hindered (i.e., where water diffuses freely but encounters barriers from which it is reflected). However, DTI does not provide a complete characterization of diffusion in the intracellular compartment of some cells, particularly myelinated axons, where water mobility is restricted by impermeable membranes (i.e., where water is trapped but otherwise free to diffuse within the cell).

The subject invention provides a new modeling framework that self-consistently describes 3-D anisotropic diffusion within a hindered extracellular compartment and within a restricted intra-axonal compartment. It results in an improved characterization and measurement tissue and cell microstructure in neuronal tissue, which promises to advance diagnosis of neurological conditions (e.g., Stroke, MS, Alzheimer’s disease), possibly cognitive and behavioral disorders (e.g., schizophrenia), as well as our ability to follow normal development and aging processes.

More specifically, this new in vivo diffusion MRI method, especially suited for the characterization of brain white matter, marries q-space and DTI concepts: Diffusion within axons is modeled as hindered diffusion parallel to the axis of the axon, and restricted diffusion perpendicular to the axis. Diffusion exterior to axons is modeled as hindered diffusion with differing diffusivities parallel and perpendicular to the nerves’ axis. To practice this method, diffusion weighted (DW) MRI data are acquired from specimens at different q-values (with different diffusion gradient magnitudes and directions). Parameters associated with tissue microstructure, such as the intra and extra-axonal principal diffusivities and their corresponding principal directions, and the volume fractions of intra and extra-axonal space are then estimated from these data. Improved angular resolution of fiber tract orientation can be obtained for tractography studies and more microstructural information can be gleaned for both diagnostic and therapeutic purposes than from conventional DTI. This technology has been named CHARMED (Composite Hindered and Restricted Model of Diffusion).

A detailed announcement describing the licensing opportunity for this and related technologies referenced below was published in the Federal Register on Tuesday, April 14, 2009 (74 FR 17199-17201). CRADA Opportunity: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Tissue Biophysics and Biomimetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel MRI methods to probe tissue structure and organization, particularly for neuroimaging applications. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or hubbsa@mail.nih.gov for more information.

Improved Expression Vectors for Mammalian Use

Mon, 04 May 2009 19:00:00 GMT
This technology relates to improving levels of gene expression using a combination of a constitutive RNA transport element (CTE) with a mutant form of another RNA transport element (RTE). The combination of these elements results in a synergistic effect on stability of mRNA transcripts, which in turn leads to increased expression levels. Using HIV-1 gag as reporter mRNA, one mutated RTE in combination with a CTE was found to improve expression of unstable mRNA by about 500-fold. Similarly this combination of elements led to synergistically elevated levels of HIV-1 Env expression. The function of CTEs and RTEs is conserved in mammalian cells, so this technology is a simple and useful way of obtaining high levels of expression of otherwise poorly expressed genes and can be used in a number of applications such as but not limited to improvements of gene therapy vectors, expression vectors for mammalian cells. CRADA Opportunity: The National Cancer Institute Vaccine Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Neuronal Decoding Algorithm for Prosthetic Limbs

Mon, 04 May 2009 23:00:00 GMT
The invention is a new algorithm for decoding neuronal responses based on the discovery that neuronal spike trains can be described using order statistics. The device has applications in the direct control of prosthetic limbs by neuronal signals originating from electrodes placed in the brain. The method allows for decoding neuronal responses by monitoring sequences of potentials from neurons while specific motor tasks are carried out. The sequences are then characterized using the innovative technique of applying order statistics to the spike train, such that subsequent action potentials representing unidentified motor tasks can be decoded to determine the unknown task. The invention is of substantial importance because it appears to have achieved a closed form interpretation of neuronal responses upon which a motor prosthetic device might be based. CRADA Opportunity: The National Institute of Mental Health, Laboratory of Neuropsychology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize decoding algorithm for neuronal responses. Please contact Suzanne Winfield at winfiels@mail.nih.gov or 301-402-4324 for more information.

Mouse Monoclonal Antibodies to Human Tristetraprolin (TTP)

Thu, 26 Mar 2009 03:00:00 GMT
TTP has been implicated in autoimmune and inflammatory diseases through its role as a regulator of the transcripts encoding several pro-inflammatory cytokines, including tumor necrosis factor alpha. However, it has been difficult to study endogenous TTP in man and other animals because it is expressed at very low levels in most cells and tissues, and because of the lack of mouse monoclonal antibodies directed at the human protein.

Scientists at the NIH have developed three mouse monoclonal antibodies (TTP-16, TTP-214 and TTP-409) that react to different regions of the human TTP to allow for the identification and localization of the TTP protein by standard protocols. Although validation has only been conducted at the level of western blotting to date, they do not appear to cross-react with other human members of the TTP protein family. CRADA Opportunity: The NIEHS, Polypeptide Hormone Action Group, of the Laboratory of Signal Transduction, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antibodies to human TTP. Please contact Dr. Elizabeth M. Denholm in the Office of Technology Transfer (denholme@niehs.nih.gov), or Dr. Perry Blackshear (black009@niehs.nih.gov) for more information.

Cell Based Immunotherapy

Wed, 25 Mar 2009 07:00:00 GMT
The invention hereby offered for licensing is in the field of Immunotherapy and more specifically in therapy of autoimmune diseases such as Type I diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosis and immune mediated allergies such as asthma as well as in transplantation-related disorders, such as graft acceptance and graft-versus-host-disease (GVHD).

While the role of FOXP3⁺ regulatory T cells (Tregs) in the maintenance of self-tolerance and immune homeostasis has been established and thus their use in adoptive immunotherapy has been contemplated, there is still no good way to purify and expand these cells in an efficient and reproducible manner ex vivo for use in human therapy. The subject invention provides a method that allows such purification for use in expansion cultures to generate sufficient numbers of cells and purity for cell-base immunotherapy. The method is based on the finding that Tregs selectively express Latency Associated Peptide (LAP) and CD121b (IL-1 Receptor Type 2) and on the ability to selectively separate these cells from other immune cells that are potentially hazardous, through the use of magnetic particles which specifically bind to either one of these two surface molecules and selectively separate those cells from the non-Tregs. CRADA Opportunity: The NIAID/NIH Laboratory of Immunology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of CD121b or LAP to produce a Treg product for cell-based immunotherapy. Please contact Nicole Mahoney at 301-435-9017 for more information.

Radiotracers for Imaging P-glycoprotein Transporter Function

Tue, 24 Mar 2009 11:00:00 GMT
This invention offers technology to help treat certain brain diseases, such as Alzheimer's disease and Parkinson's, and may lead to more effective and personalized treatments. P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established/prospective chemotherapeutics (a phenomenon known as multidrug resistance; MDR). The instant invention relates to compounds that are avid substrates for P-gp, and their preparation and use as radiotracers for imaging P-gp function in vitro and in vivo. CRADA Opportunity: The National Institute of Mental Health Molecular Imaging Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize radiotracers for imaging P-gp function. Please contact Victor Pike at pikev@mail.nih.gov for more information.

Lasonolide Compounds as Reagents for Inducing Premature Chromosome Condensation and Methods of Treating Cancer

Mon, 23 Mar 2009 15:00:00 GMT
Lasonolide A is a natural product initially isolated from an extract of the shallow water Caribbean marine sponge. The chemical structure of lasonolide A was identified in 2002, and it was chemically synthesized in 2007. The current invention discloses the discovery that lasonolide A may be used as a new reagent for inducing premature chromosome condensation in non-dividing cells; and a novel anti-proliferative and anti-metastatic agent for cancer treatment. Currently, it is difficult to analyze the cytogenetic composition of the genome of non-dividing cells because the chromosomes are loosely distributed in the nucleus, lasonolide A may be useful for performing cytogenetic studies in cells by inducing premature chromosome condensation without inducing mitosis. In addition, the invention also reveals that lasonolide A inhibits cancer cell motility. As such, lasonolide A may be used as an anti-cancer agent by itself or in combination with other anti-cancer agents such as inhibitors of topoisomerases. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Laboratory of Molecular Pharmacology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Lasonolide Compounds as Reagents for Inducing Premature Chromosome Condensation and Methods of Treating Cancer. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Gene Signature for Predicting Solid Tumors Patient Prognosis

Mon, 23 Mar 2009 19:00:00 GMT
A method of predicting the prognosis of a patient diagnosed with hepatocellular carcinoma (HCC) or breast cancer by detecting expression of one or more cancer-associated genes and a method of identifying an agent for use in treating HCC.

A progressive sequence of somatic mutations and epigenetic changes of oncogenes or tumor suppressor genes are believed to cause tumor development. However, high genomic instability in tumors causes the accumulation of genomic aberrations that do not contribute to tumor progression. Therefore, it is important to distinguish between ‘driver’ mutations that are functionally important and ‘passenger’ mutations that do not provide a selective advantage to the tumor cells.

The current invention describes a driver gene signature for predicting survival in patients with solid malignancies, including HCC and breast cancer. The gene signature includes 10 cancer-associated genes. The NIH researchers also found that these cancer-associated genes can be divided into two different groups. While a decrease in DNA copy number or mRNA expression of one group of genes is associated with poor prognosis in HCC tumors and breast cancer, such a decrease in the other group is associated with good prognosis. The inventors have also demonstrated that at least four of these cancer-associated genes are functional tumor suppressor genes. Thus, these genes may be molecular targets of HCC and breast cancer. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research, Laboratory of Human Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this Gene Signature for Predicting Hepatocellular Carcinoma Patient Prognosis. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Dendrimer Conjugates in the Treatment of Neurodegenerative Diseases, Stroke, Epilepsy, and Pain

Mon, 23 Mar 2009 23:00:00 GMT
Conjugate compositions useful in the treatment of a variety of diseases, comprising a dendrimer and a ligand. The ligand is a functionalized congener of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily. More specifically, the invention focuses on several agonists and antagonists of A₁, A_2A, A_2B, and A₃ adenosine receptors and P2Y receptors, all members of the GPCR superfamily. For example, an agonist of the A₁ adenosine receptor is useful for treating a number of diseases including neurodegeneration, stroke, epilepsy, and pain. Antithrombotic treatment is another example of the use of this dendrimer technology. Dendrimers are polymers made from branched monomers through the iterative organic synthesis by adding one layer at each step to provide a symmetrical structure. Certain drugs, such as taxol, cisplatin, methotrexate, and ibuprofen, have been covalently linked to dendrimers in a reversible fashion. However, dendrimer conjugates in this application are biologically active without cleavage of the drug or cellular uptake. The conjugate of the invention can include any suitable dendrimer, particularly a poly(amidoamine) (PAMAM) dendrimer. The invention further provides pharmaceutical compositions and methods of treating various diseases and diagnostic methods employing such conjugates. CRADA Opportunity: The NIDDK Laboratory of Bioorganic Chemistry is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize dendrimer conjugates of suitably functionalized small molecule ligands of adenosine receptors and P2Y nucleotide receptors. For collaboration opportunities, please contact Dr. Kenneth A. Jacobson at kajacobs@helix.nih.gov or 301-496-9024.

Treatment of Schistosomiasis Using Substituted Oxadiazole 2-Oxides

Tue, 24 Mar 2009 03:00:00 GMT
Available for licensing and commercial development are pharmaceutical compositions and methods for the treatment of Schistosomiasis in mammals. The various compositions are based on a number of compounds derived from 1,2,5-oxadiazole that are potent inhibitors of thioredoxin glutathione reductase (TGR), a critical parasite redox protein.

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma, including S. mansoni, S. japonicum and S. haematobium. Adult schistosome parasites live in an aerobic environment within human hosts, and therefore must have effective mechanisms to maintain cellular redox balance. Additionally, the worms must be able to evade reactive oxygen species generated by the host's immune response. In most eukaryotes there are two major systems to detoxify reactive oxygen species, one based on the tripeptide glutathione and the other based on the protein thioredoxin. Glutathione reductase (GR) reduces glutathione disulfide, whereas thioredoxin reductases (TrxR) are pivotal in the Trx-dependent system. It was recently discovered that specialized TrxR and GR enzymes are absent in schistosomes. Instead, they are replaced by the unique multifunctional enzyme TGR. This reliance on a single enzyme for both glutathione disulfide and thioredoxin reduction suggests that the parasite's redox systems are subject to a bottleneck dependence on TGR, and that TGR represents a potentially important drug target.

Schistosomiasis remains a major and neglected health problem in many tropical areas. The health burden resulting from Schistosomiasis is estimated to include more than 200 million people infected, 779 million at risk of infection, 280,000 deaths annually, and more than 20 million individuals experiencing high morbidity. Clinical manifestations of schistosomiasis infection include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. The primary route of infection occurs through contact with infected river and lake water, at which time the parasite burrows into the skin, matures, then migrates to other areas of the body. Adult schistosome parasites reside in the mesenteric veins of their human hosts, where they can survive for up to 30 years. The need to control schistosomiasis is acute and efforts have been ongoing for years on three main fronts: prevention (via establishment and maintenance of sources of safe potable water), development of a vaccine, and use of drugs to treat the infection. CRADA Opportunity: The NIH Chemical Genomics Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize appropriate lead compounds described in U.S. Provisional Application No. 61/088,970. Please contact Dr. Craig J. Thomas via e-mail (craigt@nhgri.nih.gov) for more information.

Anti-Hepatitis C Virus Activity of the Protein Scytovirin (SVN)

Mon, 23 Mar 2009 07:00:00 GMT
The invention provides compositions and methods of use for potent anti-HCV protein scytovirin to prevent and treat HCV infections. Currently there is neither effective treatment nor vaccine against HCV infection and chronic HCV infection may lead to liver cancer and death. Scytovirin can be used alone or in combination with other anti-HCV drugs for HCV treatment and prevention. CRADA Opportunity: The National Cancer Institute CCR Molecular Targets Development Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Method of Making a Vaccine

Fri, 20 Mar 2009 11:00:00 GMT
Current invention describes the methods to prepare vaccines, and to use such vaccines in the vaccination and treatment of human disease, e.g., the human immunodeficiency virus (HIV) infections and cancer. More specifically, the present invention provides a vaccine and method for making same which is effective to elicit a desired antibody against a target antigen comprising a primary immunogen and a secondary immunogen, wherein the primary immunogen is effective to elicit B cell receptors (BCRs) that are on the maturational pathway of the desired antibody and have an intermediate degree of somatic mutational diversity, and the secondary immunogen comprises an epitope of the desired target antibody and is effective to further diversify the BCRs sufficient to form mature BCRs having the identical or substantially identical sequence as the desired antibody. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this method. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Prevention of Head and Neck Cancer Using Rapamycin and Its Analogs

Wed, 25 Feb 2009 16:00:00 GMT
It is frequently observed in head and neck squamous cell carcinoma (HNSCC), a cancer occurring mostly in the mouth, that the Akt/mTOR pathway is abnormally activated. Therefore, inhibiting this signaling pathway may help in treating this disease. Rapamycin and its analogs are known to inhibit the activity of mTOR so in principle they could serve as therapeutics for treating HNSCC.

Researchers at the NIH have developed a method of potentially preventing or treating HNSCC through the inhibition of mTOR activity. The proof of this principle was demonstrated by rapid regression of mouth tumors in mice afflicted with Cowden syndrome with the administration of rapamycin. Like HNSCC, development of this disease is linked to over activation of the Akt/mTOR pathway. Furthermore, the therapeutic potential of rapamycin was demonstrated using mice in experiments that model chronic exposure to tobacco, which promotes the development of HNSCC. Therefore, inhibitors of mTOR have considerable potential in the prevention and treatment of HNSCC. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Oral and Pharyngeal Cancer Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at bradleyda@nidcr.nih.gov for more information.

Compositions and Methods for Vaccine and Virus Production

Tue, 17 Feb 2009 21:00:00 GMT
This technology relates to compositions and methods for improving the growth characteristics of cells engineered to produce live viruses such as the Influenza virus. Featured is a method that uses the gene candidate, siat7e, or its expressed or inhibited products in Madin Darby Canine Kidney (MDCK) cells. The gene expression modulates anchorage-dependence of the cell line thereby allowing scale-up on bioreactor platforms without the use of microcarrier beads and reducing production costs. More specifically, this technology claims use of the methods embodied in the patent application for production of the Influenza viruses (human, avian and canine). CRADA Opportunity: The Biotechnology Core laboratory will consider collaborative research to further develop, evaluate, or commercialize the above invention. Please contact Dr. Joseph Shiloach at joseph.shiloach@nih.gov or 301-496-9719 for more information.

Microwave-Assisted Freeze Substitution of Biological and Biomedical Samples

Wed, 18 Feb 2009 02:00:00 GMT
Freeze substitution fixation (FS) of hydrated samples frozen in vitreous ice provides exceptional preservation of structure for light and electron microscopy, and enables immunological detection of thermo-labile antigens that otherwise are damaged/destroyed by processing at ambient or elevated temperatures. Its use as a research tool or in clinical pathology has, however, been limited by the relatively lengthy periods required for passive diffusion of fixatives and organic solvents into the frozen hydrated material.

The invention utilizes controlled microwave (MW) irradiation to accelerate the FS process; and comprises systems, devices and methods for microwave-assisted processing of samples under cryo-conditions. The entire MWFS procedure has been accomplished in less than 4 hours as compared to the approximately 2-5 days required for FS. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Research Technologies Branch, Electron Microscopy Unit, is interested in collaborative research to further develop, evaluate, or commercialize potential applications of this invention, including design and development of instrumentation for conducting MWFS. Please contact Barry U. Buchbinder, Ph.D., NIAID/OTD, at 301-594-1696 or bbuchbinder@niaid.nih.gov, for more information.

In Vivo Quantitative Tissue Oxygen Imaging Using Pulsed Time-Domain Electron Paramagnetic Resonance - Echo-based Single Point Imaging (ESPI)

Tue, 17 Feb 2009 07:00:00 GMT
Available for licensing and commercial development are patent rights covering an EPR image formation strategy for in vivo imaging of physiological function. It emphasizes image resolution and quantitative assessment of in vivo tissue oxygen that are important in planning radiation and chemotherapeutic treatments for patients with cancers. The method pertains exclusively to time-domain Fourier Transform EPR imaging (FT-EPRT) with emphasis on spatial and temporal resolution, since physiological processes are generally rapid and require accurate and rapid time-course information.

Two most important existing methods are Spin Echo Fourier (SEF) and Single Point Imaging (SPI). ESPI (Echo-based Single Point Imaging) enables the combination of the advantages of the quantitative T2 contrast of SEF strategy and the super high resolution of the SPI methodology, leading to reliable EPR imaging for tissue physiological function in vivo. CRADA Opportunity: The National Cancer Institute Radiation Biology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Echo-based Single Point Imaging. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Quantitative Real-Time RT-PCR Array for Detection of Human Herpesvirus 6A Gene Expression

Tue, 17 Feb 2009 12:00:00 GMT
This invention describes an RT-PCR array that allows for the simultaneous transcriptional profiling of the human herpesvirus HHV6A genome. It may be used to determine the contribution of HHV6A to the development of lymphomas, other types of cancer or diseases where an infectious agent is suspected. Primer pairs are designed to amplify under identical reaction conditions and are rigorously tested to ensure specificity for the HHV6A ORFs to the exclusion of all other human herpesviruses including HHV6B and HHV7.

Recent findings of the association of active viral genes with cancer cells have led to new proposed targets for cancer vaccines and therapeutics. The ability to distinguish HHV6A from other related herpesviruses, and to independently assay viral gene activity, may lead to the identification of new viral targets for the treatment of cancers and other diseases where HHV6A transcription is active. CRADA Opportunity: The National Cancer Institute, Advanced Technology Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize virus specific quantitative real-time RT-PCR arrays. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Sialostatin Mediation Controls Blood-feeding Success of the Tick Ixodes scapularis

Mon, 02 Feb 2009 17:00:00 GMT
This invention offers an environmentally friendly alternative to existing acaricides (pesticides), and relates to vaccines against tick bites and the pathogens that the ticks may transmit.

Bites from the nymphal stage of Ixodes scapularis are associated with Lyme disease transmission in disease-endemic areas of central and eastern US. Ixodes scapularis nymphs are the key vector stage implicated in Lyme disease transmission, mainly due to their small size that makes timely detection difficult. Guinea pig vaccination against sialostatin L2, a secreted Ixodes scapularis salivary protein, can confer nymphal recognition and protection against the tick. Increased rejection rates, prolonged feeding time, and inflammation were observed in the vaccine group, indicating that a protective host immune response was elicited. Moreover, anti-sialostatin L2 titers correlate with weight reduction of nymphs by the end of feeding. These studies suggest that an essential action of sialostatin L2 can be blocked by host humoral immunity. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases / Laboratory of Malaria and Vector Research / Vector Biology Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize potential applications based on the above mentioned patent and in regard to the protection from tick bites and the pathogens they transmit. Please contact Charles Rainwater, NIAID/OTD, at 301-435-8617/or crainwater@niaid.nih.gov for more information.

Humanized Monoclonal Antibodies that Specifically Bind Japanese Encephalitis Virus (JEV) and Their Use

Mon, 02 Feb 2009 22:00:00 GMT
Japanese encephalitis virus (JEV) is the prototype virus of the Japanese encephalitis (JE) group belonging to the Flavivirus genus of the Flaviviridae family. Other members of the group include Kunjin virus, St. Louis encephalitis virus, and West Nile encephalitis virus (WNV). JEV is widely distributed in South Asia, Southeast Asia, and the Asian Pacific Rim. In recent years, JE epidemics have spread to previously unaffected areas, such as northern Australia, Pakistan, India and Indonesia. The JE outbreak in India during July to November of 2005 was the longest and most severe in recent years, affecting more than 5,000 persons and causing more than 1,000 deaths. It is estimated that JEV causes 35,000 to 50,000 cases of encephalitis, including 10,000 deaths and as many neurologic sequelae, each year. The wide geographical distribution and the existence of multiple strains, coupled with the high rate of mortality and residual neurological complications in survivors, make JEV infection an important public health problem. Until a JEV vaccine becomes generally available, passive immunization with potently neutralizing anti-JEV antibodies remains an attractive strategy for short-term prevention of and therapeutic intervention in encephalitic JEV infections.

From a panel of 11 Fabs recovered by different panning strategies, three highly potent neutralizing antibodies, termed Fabs A3, B2, and E3, which recognized spatially separated regions on the JEV virion were identified. These antibodies reacted with epitopes in different domains: the major determinant for Fab A3 was Lys179 (domain I), that for Fab B2 was Ile126 (domain II), and that for Fab E3 was Gly302 (domain III) in the envelope protein, suggesting that these antibodies neutralize the virus by different mechanisms. These three Fabs and derived humanized monoclonal antibodies (MAbs) exhibited high neutralizing activities against a broad spectrum of JEV genotype strains. In preclinical testing, the monoclonal antibodies of the technology significantly prolonged the average survival time compared to the control group, suggesting a therapeutic potential for use of MAb B2 in humans.

This application claims the antibodies described above, methods of preventing and/or treating JEV with the antibodies, and diagnostics using the antibodies of the technology. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize "Humanized Monoclonal Antibodies that Specifically Bind Japanese Encephalitis Virus (JEV) and Their Use". Please contact Percy Pan at 301-451-3523 for more information.

Adoptive Immunotherapy for Reestablishing HIV-specific Cytotoxic T-cell (CD8 T-cell) Function in HIV and AIDS Patients and Methods for Assessing the Reestablishment of CD8 T-cell Function

Tue, 03 Feb 2009 03:00:00 GMT
This technology includes methods and compositions for rescuing or reestablishing the ability of HIV-specific, cytotoxic T-cells (CD8 T-cells) to proliferate and kill HIV-infected cells such as CD4 cells. Additionally, this invention provides a means for evaluating the ability of therapeutic vaccines or other therapies to reestablish CD8 T-cell function during HIV infection. As an immunotherapy, this technology involves treating peripheral blood mononuclear cells (PBMCs) from an HIV or AIDS patient to reestablish CD8 T-cell function and returning the treated cells to the patient. It is anticipated that this technology could provide an alternative to antiretroviral therapy (ART).

Background:
This technology arose from research aimed at understanding why HIV infection does not progress in a subset of HIV-infected individuals, called long-term nonprogressors (LTNP). During the course of HIV infection HIV-specific CD8 T-cells from HIV progressors lose the ability to proliferate and kill HIV-infected cells using cytotoxins such as perforin and granzymes A and B. Unlike HIV progressors, it has been shown that CD8 T-cells from LTNP retain the ability to proliferate and use cytotoxins to kill HIV-infected cells. This technology provides a means for rescuing HIV-specific CD8 T-cell proliferation and cytotoxic functions in HIV progressors. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Richard Williams at 301-451-3522 for more information.

HTLV-II Vector and Methods of Use

Mon, 02 Feb 2009 08:00:00 GMT
The invention hereby offered for licensing is in the field of vaccines and vaccine vectors. More specifically the invention provides compositions and methods of use of HTLV-II viral vector. The vector comprises at least a portion of the HTLV-II genome encoding the gag, pro, and pol genes and lacking all or a portion of the pX region. A heterologous gene is inserted within the deletion of the pX region. The gene of interest may encode all or a portion of a protein that corresponds to a viral protein of a foreign virus. The viral vectors thus constructed are useful for inducing immune response to the viral protein from the foreign virus. In particular the invention claims vaccines against HIV and SIV. CRADA Opportunity: The National Cancer Institute, Animal Models & Retroviral Vaccine Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HTLV-II vectored HIV vaccines. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Mouse Monoclonal Antibodies to MAD1, a Human Spindle Assembly Checkpoint Protein for Maintaining Chromosomal Segregation

Mon, 02 Feb 2009 13:00:00 GMT
Scientists at the National Institutes of Health have developed mouse monoclonal antibodies against the human spindle assembly checkpoint protein, MAD1. The spindle assembly checkpoint in mitotic cell division regulates the fidelity of chromosome segregation during cell division. MAD1 is an important component of this checkpoint control, which if compromised, can lead to the initiation of cancer cell growth. These monoclonal antibodies are the first available antibodies against MAD1 and can be used in laboratory research and diagnostics. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize reagents for studying cell cycle checkpoint factors. Please contact Agnes Rooke at rookeab@niaid.nih.gov or by phone at 301-594-1697 for more information.

Novel Protein Delivery System for Mammalian Cells

Mon, 02 Feb 2009 18:00:00 GMT
Virus-like particles (VLPs) consist of viral structural proteins that are capable of self-assembly into a nanoparticle, but are non-infectious because they lack viral nucleic acids. VLPs have been used in viral vaccines, such as those for human papilloma virus and hepatitis B. However, they also have great potential in other applications, such as cancer vaccines, transport of nucleic acids into target cells (gene therapy), and transport of biologics or other large molecules into target cells for therapeutic purposes. The present technology discloses a chimeric VLP containing a GAG-Cre recombinase fusion protein. This recombinase fusion protein retains Cre recombinase activity, and can excise a LOX-flanked gene in a transduced target cell. Experiments by Drs. Kaczmarczyk and Chatterjee have demonstrated that chimeric VLPs can be used to deliver functional fusion proteins into cells. The technology also provides for a two-VLP protein delivery system designed to deliver a protein of interest into a target cell. The present technology also discloses VLPs containing GAG-protein of interest (ex. GAG-Cre) co-packaged with GAG-protease to deliver protein of interest in target site as a fully-processed protein rather than as a fusion protein.

The claims in the pending patent application provide for virus like particles, methods of making virus like particles, and methods of using virus like particles to deliver proteins to a cell. The claims also provide for methods of targeting a protein to a cell, methods of protein therapy and methods of treating diseases or disorders. CRADA Opportunity: The National Cancer Institute Advanced Technology Program, Protein Expression Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Substituted IL-15

Mon, 02 Feb 2009 23:00:00 GMT
Interleukin-15 (IL-15) is an immune system modulating protein (cytokine) that stimulates the proliferation and differentiation of T- lymphocytes. In the clinical context, IL-15 is being investigated for use in the treatment of diseases such as cancer. In vitro manufacture of IL-15 can be problematic.

The invention relates to substituted IL-15 amino acid sequences of one or more amino acids that are predicted to reduce or eliminate deamidation of a specific aspargine amino acid residue found within the IL-15 protein. Deamidation can lead to protein degradation and interfere with the pharmaceutical purification and processing of IL-15. The invention also provides potential substituted gene sequences that encode the substituted IL-15 amino acid sequences. The substituted IL-15 amino acid sequences may advantageously facilitate the refolding, purification, storage, characterization, and clinical testing of IL-15. CRADA Opportunity: The National Cancer Institute Biological Research Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the topic of this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

HMGN Polypeptides as Immune Enhancers and HMGN Antagonists as Immune Suppressants

Tue, 03 Feb 2009 04:00:00 GMT
HMGN polypeptides are multidomain proteins known to function by binding DNA to regulate the transcription of certain genes inside cells. However, when a HMGN polypeptide is released extracellularly, it distinctly acts as a potent activator of the immune system. Because of this activity, it has potential use as a biological therapeutic for stimulating an immune response as well as a promising target for antagonist drugs to suppress a pathological inflammatory response.

Secreted HMGN acts as a potent recruiter and activator of dendritic cells, the cell principally responsible for initiating the immune response. Furthermore, it enables dendritic cells to preferentially induce a Th1-type T lymphocyte response that leads to enduring cellular immunity. Therefore, HMGN has potential use as a clinically effective immunoadjuvant for use in vaccines against tumors and many intracellular pathogens.

Investigators at the National Institutes of Health have developed compositions and methods for using HMGN and its derivatives as immunoadjuvants in combination, as mixtures or as chemical conjugates, with microbial or tumor antigens. HMGN has the advantage of being gene encoded so it can be fused to an antigen gene to produce recombinant fusion proteins or administered as a DNA vaccine. Conversely, HMGN could be exploited as a drug target to treat diseases that would benefit from shifting away the Th1-type immune response towards a Th2-type or humoral immune response. This would be beneficial for treatment of parasitic infections and inflammatory or autoimmune disorders. CRADA Opportunity: The National Cancer Institute Laboratory of Molecular Immunoregulation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HMGN1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.

Prognostic Test for Breast Cancer Based on a 12 Gene Expression Signature

Mon, 02 Feb 2009 09:00:00 GMT
The clinical course and survival times of patients with breast cancer varies greatly, consequently it is difficult to establish a prognosis for the disease. To improve patient prognosis, much effort has been made to identify biological markers that would allow precise staging of the cancer. When cells cannot repair minor damage to their DNA it leads to genetic instability which can produce gross abnormalities in chromosomes and the onset of a cancer. It is known that the magnitude of the abnormalities is strongly correlated with a negative prognosis for cancer. Thus, genetic instability can serve as a useful biomarker for establishing a prognosis for breast cancer patients. Presently, genetic instability is not directly accounted for in established prognostic tests.

Investigators at the National Cancer Institute (NCI) have developed a compact gene signature that detects genome instability in breast cancer cells. By comparing changes in expression levels of only 12 genes in malignant tissue to levels in normal breast tissue it is possible to detect the genetic abnormalities that are indicative of a poor prognosis. This method has potential to improve markedly the forecasting of clinical outcomes for breast cancer and help improve treatment of this disease. CRADA Opportunity: The National Cancer Institute Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Prognostic Test for Breast Cancer Based on a 12 Gene Expression Signature. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Attenuated Salmonella as a Delivery System for siRNA-Based Tumor Therapy

Fri, 09 Jan 2009 14:00:00 GMT
The discovery that genes vectored by bacteria can be functionally transferred to mammalian cells has suggested the possible use of bacterial vectors as vehicles for gene therapy. Genetically modified, nonpathogenic bacteria have been used as potential antitumor agents, either to elicit direct tumoricidal effects or to deliver tumoricidal molecules. Bioengineered attenuated strains of Salmonella enterica serovar typhimurium (S. typhimurium) have been shown to accumulate preferentially greater than one-thousand fold in tumors than in normal tissues and to disperse homogeneously in tumor tissues. Preferential replication allows the bacteria to produce and deliver a variety of anticancer therapeutic agents at high concentrations directly within the tumor, while minimizing toxicity to normal tissues. These attenuated bacteria have been found to be safe in mice, pigs, and monkeys when administered intravenously, and certain live attenuated Salmonella strains have been shown to be well tolerated after oral administration in human clinical trials. The S. typhimurium phoP/phoQ operon is a typical bacterial two-component regulatory system composed of a membrane-associated sensor kinase (PhoQ) and a cytoplasmic transcriptional regulator. phoP/phoQ is required for virulence, and its deletion results in poor survival of this bacterium in macrophages and a marked attenuation in mice and humans. phoP/phoQ deletion strains have been employed as effective vaccine delivery vehicles. More recently, attenuated salmonellae have been used for targeted delivery of tumoricidal proteins.

This technology comprises live, attenuated Salmonella strains as a delivery system for small interfering double-stranded RNA (siRNA)-based tumor therapy. The inventors' data provide the first convincing evidence that Salmonella can be used for delivering plasmid-based siRNAs into tumors growing in vivo. Claimed in the related patent application are methods of inhibiting the growth or reducing the volume of solid cancer tumors using the si-RNA constructs directed against genes that promote tumor survival and cancer cell growth. The Stat3-siRNAs carried by an attenuated S. typhimurium described in the application exhibit tumor suppressive effects not only on the growth of the primary tumor but also on the development of metastases, suggesting that an appropriate attenuated S. typhimurium combined with the RNA interference (RNAi) approach may offer a clinically feasible method for cancer therapy. CRADA Opportunity: FDA-CBER Division of Bacterial, Parasitic, and Allergenic Products is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Salmonella-delivered anti-tumor therapies or Salmonella-vectored vaccines. Please contact Alice Welch at Alice.Welch@fda.hhs.gov for more information.

Method of Treating Pneumoconiosis with Oligodeoxynucleotides

Fri, 09 Jan 2009 19:00:00 GMT
The inhalation of dust containing crystalline silica particles causes silicosis, an incurable lung disease that progresses even after dust exposure ceases. The World Health Organization estimates that over a million US workers are exposed to silica dust annually, and that thousands worldwide die each year from silicosis. The pulmonary inflammation caused by silica inhalation is characterized by a cellular infiltrate and the accumulation of chemokines, cytokines (including TNF-alpha, IL-1, and IL-6), and Reactive Oxygen Species (ROS) in bronchoalveolar lavage (BAL) fluid.

Macrophages are the predominant immune cell type present in alveolar spaces where they play an important role in the lung pathology associated with silica inhalation. The uptake of silica particles by macrophages triggers the production of ROS (including hydrogen peroxide) via the oxidative stress pathway, which in turn contributes to pulmonary damage and macrophage death.

One potential strategy for limiting the production of proinflammatory cytokines and ROS after silica exposure involves treatment with "suppressive" oligonucleotides (ODN). Suppressive ODN express motifs based on the repetitive TTAGGG hexamers present at high frequency in the telomeric ends of self DNA. Previous studies showed that these motifs (released by injured host cells) block Th1 and proinflammatory cytokine production in vitro and down-modulate over-exuberant/pathologic immune responses in vivo (such as those found in septic shock and autoimmune diseases).

This application claims methods for treating, preventing or reducing the risk of developing occupational lung diseases using. Preclinical in vivo studies show that pretreatment with suppressive (but not control) ODN reduces silica-dependent pulmonary inflammation. Preclinical in vivo studies also showed that treatment with suppressive ODN also reduced disease severity and improved the survival of mice exposed to silica. CRADA Opportunity: The National Cancer Institute, Laboratory of Experimental Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Method of Treating Pneumoconiosis with Oligodeoxynucleotides. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Use of Mono-Amine Oxidase Inhibitors to Prevent Herpes Virus Infections and Reactivation from Latency

Sat, 10 Jan 2009 00:00:00 GMT
Available for licensing are methods of using Monoamine Oxidase Inhibitors (MAOIs) to prevent alpha-herpesvirus lytic infections, such as those caused by Herpes simplex virus (HSV-1 or HSV-2) and Varicella zoster virus (VZV), and to possibly prevent the periodic reactivation of these viruses from latency. MAOIs have been historically used to treat depression, hypertension, and related diseases. The invention describes how MAOIs can also inhibit LSD1, a histone/protein demethylase that is required for initiation of alpha-herpesvirus lytic infection. After an initial lytic infection, alpha-herpesviruses establish latent infections in sensory neurons and undergo periodic reactivation that results in disease ranging from mild lesions to life threatening encephalitis. Investigators have determined that MAOIs may also block the reactivation process. Due to the nature of the target LSD1 and its role in modulating chromatin modifications, these drugs could also prevent infection by or reactivation of other nuclear viruses.

Alpha-herpesviruses infections are common worldwide, with 57% to 80% of adults being seropositive for HSV. Recurrent labial herpes affects roughly one third of the U.S. population, and these patients typically experience 1 to 6 episodes per year. Genital herpes can result from infection with either HSV type and HSV-1 has become an important cause of genital herpes in some developed countries. HSV keratitis is the most frequent cause of corneal blindness in the United States, is a leading indication for corneal transplantation, and is the most common cause of infectious blindness in the Western world. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases' Laboratory of Viral Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of MAOIs to prevent herpes virus infections and reactivation from latency. Please contact Thomas Kristie, PhD at 301.496.3854 or tkristie@niaid.nih.gov for more information.

Recombineering Vector

Mon, 05 Jan 2009 05:00:00 GMT
Transgenic mouse models have become a common experimental tool for unraveling gene function. Bacterial artificial chromosome (BAC) mediated transgenesis has proven to be a highly reliable way to obtain accurate transgene expression for in vivo studies of gene expression and function. A rate-limiting step in characterizing large numbers of genes by this approach has been the speed and ease by which BACs can be modified. NIH investigators have developed a highly efficient recombineering vector that can be used for modifying BACs in bacteria. This new vector contains tetracycline and chloramphenical resistance as well as the ccdB gene that encodes a protein that interferes with E. coli DNA gyrase. This vector can be propagated in ccdB resistant E. coli strains but not in other strains (DH5a, Top10, DH10B, etc) unless the ccdB is replaced by DNA inserts flanked by attB1 and attB2 sites. This vector was generated to modify BAC plasmids by RecA-mediated recombination.

The vector disclosed here bypasses the rate-limiting step in recombineering protocols; the efficient cloning of a modifying vector. It is well suited for efficient production of engineered BACs for use in a variety of in vivo studies. CRADA Opportunity: The NIAMS/NIH Genomics and Immunity group is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the engineering of mouse transgenic constructs using the new vector and BAC recombineering. Please contact Rafael Casellas, Ph.D. at 301-402-7858 or email to casellar@mail.nih.gov for more information.

Knockout of Aryl Hydrocarbon Receptor (AhR) and its Binding Partner Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) each in Separate Mouse Models

Mon, 05 Jan 2009 10:00:00 GMT
The technology relates to two separate knockout mouse models of related transcription factors that bind each other. The aryl hydrocarbon receptor (AhR) and the aryl hydrocarbon receptor nuclear translocator (Arnt) protein are transcription factors that play an important role in mediating the effects of man-made environmental toxins. They also play a role in mammalian development and physiological homeostasis. Members of the PAS domain/bHLH family of transcription factors, they are obligate dimerization partners with each other and other members of this family, such as hypoxia-inducible factor 1alpha (HIF1alpha). These transcription factors have been shown to be important in a number of specific tissues including ovary, vascular endothelium, keratinocytes, T-cells, and liver.

Available for licensing is a knockout mouse line in which the AhR receptor has been knocked-out, and a mouse line containing a floxed allele of the Arnt gene. The Arnt mouse line can be used to disrupt the Arnt gene in different tissues by breeding the Arnt-floxed mice with transgenic mice in which the Cre recombinase is under the control of tissue-specific promoters. These mice may be used as a research tool for drug development where PAS/bHLH transcription factors are targeted. CRADA Opportunity: The National Cancer Institute, Laboratory of Metabolism, Center for Cancer Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Method for Predicting and Detecting Tumor Metastasis

Mon, 05 Jan 2009 15:00:00 GMT
Detecting cancer prior to metastasis greatly increases the efficacy of treatment and the chances of patient survival. Although numerous biomarkers have been reported to identify aggressive tumor types and predict prognosis, each biomarker is specific for a particular type of cancer, and no universal marker that can predict metastasis in a number of cancers have been identified. In addition, due to a lack of reliability, several markers are typically required to determine the prognosis and course of therapy.

The inventors discovered a novel CPE splice variant designated CPE-deltaN and found its expression levels increase according to the presence of cancer and metastasis wherein this variant is upregulated in tumors and further increased in metastatic cancer. This data has been demonstrated both in vitro and in vivo experiments and in liver, breast, prostate, colon, and head and neck cancers. Metastatic liver cells treated with CPE-deltaN siRNA reversed the cells from being metastatic and arrested cells from further metastasis. Thus, this novel CPE isoform is a biomarker for predicting metastasis and its inhibitors have an enormous potential to increase patient survival. CRADA Opportunity: The National Institute of Child Health and Human Development, Laboratory of Development Neurobiology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Method for Predicting and Detecting Tumor Metastasis. Please contact Joseph M. Conrad, LD, PhD, at 301-435-3107 or jmconrad@mail.nih.gov for more information.

Novel Inhibitor of NF-kappa B Pathway

Mon, 05 Jan 2009 20:00:00 GMT
Many tumors and blood cell cancers show overactivation of the NF-kappa B signal transduction pathway. This overactivation is associated with cancer forming in the colon, liver and other epithelial sites. In addition, there is evidence that overactivation leads to tumor formation and metastasis. However, this pathway is key for normal immunity, so any inhibition of NF-kappa B overactivation must avoid diminishing the body’s ability to fight infection.

This invention claims a compound that inhibits NF-kappa B activation without affecting other transcription factors such as AP-1 and SRE binding proteins. It appears to function by blocking IKK beta and is effective at low micromolar concentrations without affecting cell proliferation or cell survival. At this low concentration, NF-kappa B is reduced to basal levels so this novel compound has prospects for preventing or treating cancer without being detrimental to immunity. In addition, because NF-kappa B overactivation contributes to a variety of inflammatory disorders including colitis, diabetes, prostatitis, and pancreatitis this compound has therapeutic applications beyond cancer. CRADA Opportunity: The National Cancer Institute (SAIC-Frederick) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize around development of analogs and/or further investigations of mechanism of action of the compound. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Method of Promoting Hematopoietic Stem Cell Engraftment by Enhancement of CXCR4 Activity

Fri, 02 Jan 2009 01:00:00 GMT
The success of allogeneic Hematopoietic Stem Cell (HSC) transplant is dependent upon factors affecting engraftment of donor HSC. Engraftment is affected by type and intensity of bone marrow conditioning and immunosuppression achieved by chemotherapy or radiation treatments as well as the number of stem cells present in the graft. Factors influencing HSC trafficking, such as HSC chemotaxis and adhesion, modulate the ability of HSCs to engraft in the transplant recipient. Chemokine receptor CXCR4 (present on HSC) and its ligand, SDF-1, play an important role in attracting HSC to and retaining HSC in the bone marrow after transplantation. Studies indicate that with increased amounts of CXCR4 in human HSC there is a several fold increase in the engraftment of HSCs in a xenograft mouse transplant model.

This technology is directed to compositions comprising HSCs and methods for promoting CXCR4 expression in a HSC by inhibiting GRK3 or GRK6 (G-protein coupled receptor kinase (GRK) regulators of CXCR4) with an antisense compound. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Host Defenses, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a method to improve hematopoietic stem cell transplantation through the enhancement of CXCR4 activity. Please contact Rosemary C. Walsh, Ph.D. at 301-451-3528 or rcwalsh@niaid.nih.gov for more information.

A Novel and Efficient Technology for Targeted Delivery of siRNA

Thu, 01 Jan 2009 06:00:00 GMT
The biological phenomenon of RNA interference (RNAi) has much promise for developing therapeutics to a variety of diseases. However, development of RNAi therapies remains mainly in preclinical stages largely because of difficulties in delivering small inhibitory RNAs (siRNA) and short hairpin RNAs (shRNA) into target cells. Although viral vector-based siRNA delivery systems have been widely used, their specificity and safety remains significant issue. Without a solution to this delivery problem, RNAi cannot fulfill its therapeutic promise.

Investigators at the National Institutes of Health have developed novel compositions and methods for delivering inhibitory oligonucleotides to cells in a targeted and efficient manner. The compositions and methods are based on utilizing a cell surface receptor targeting ligand, such as cytokine or chemokine, and a domain that binds an inhibitory oligonucleotide, to efficiently deliver the inhibitory oligonucleotide to the cell that expresses the cell surface receptor targeting ligand. Chemokine receptors are differentially expressed on various cells, including tumors; hence this technology allows targeting siRNA to aberrant cells. Gene silencing can also be achieved in variety of immune cells by targeting cytokine receptors. This technology has great potential for developing into a safe and effective means of delivering therapeutic siRNAs. CRADA Opportunity: The National Institute on Aging, Immunotherapeutics Unit, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize chemokine-based siRNA/shRNA technology for treatment of cancers and autoimmune diseases, i.e. to control expression of immunomodulatory cytokines and other factors that facilitate tumor escape, activity of regulatory T cells or Th2 type of cells. This technology can be also utilized to boost vaccine responses against cancers and chronic infectious diseases. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Monoclonal Antibodies to the Tumor-Specific Antigen, Human ROR1

Thu, 01 Jan 2009 11:00:00 GMT
B-cell chronic lymphocytic leukemia (B-CLL) is an incurable disease developed by more than 15,000 Americans each year and currently, there are no therapeutic monoclonal antibodies (mAbs) that specifically recognize B-CLL tumor cells. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a constitutively expressed tumor-specific cell surface antigen and an ideal target for therapeutic antibodies.

Available for licensing are mouse anti-human ROR1 monoclonal antibodies (hybridomas designated 2D11, 1A1, and 1A7). All mAbs bind to ROR1 on the surface of primary human B-CLL cells and have good potential for therapeutic development by either humanization, conversion to chimeric mouse/human antibodies, or conjugation to a radioisotope, chemical drug or bacterial toxin to B-CLL and breast cancer. CRADA Opportunity: The National Cancer Institute, Experimental Transplantation and Immunology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic or therapeutic mAbs against ROR1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Mice with a Conditional LoxP-Flanked Glucosylceramide Synthase Allele Controlling Glycosphingolipid Synthesis

Thu, 01 Jan 2009 16:00:00 GMT
Glycosphingolipids are organizational building blocks of plasma membranes that participate in key cellular functions, such as signaling and cell-to-cell interactions. Glucosylceramide synthase - encoded by the Ugcg gene - controls the first committed step in the major pathway of glycosphingolipid synthesis. Global disruption of the Ugcg gene in mice is lethal during gastrulation. The inventors have established a Ugcg allele flanked by loxP sites (floxed). When cre recombinase was expressed in the nervous system under control of the nestin promoter, the floxed gene underwent recombination, resulting in a substantial reduction of Ugcg expression and of glycosphingolipid ganglio-series levels. The mice deficient in Ugcg expression in the nervous system show a striking loss of Purkinje cells and abnormal neurologic sphingo-lipid behavior.

The Research Tools available are mice with a floxed Ugcg allele that can be deleted in a conditional manner. These mice carrying floxed Ugcg alleles will be useful for delineating the functional roles of glycosphingolipid synthesis in the nervous system and in other physiologic systems.

CRADA Opportunity: The NIDDK Genetics of Development and Disease Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the sphingolipid metabolism in physiology and disease. Please contact Dr. Proia at proia@nih.gov for more information.

Method for Predicting and Detecting Tumor Metastasis

Mon, 15 Dec 2008 21:00:00 GMT
Detecting cancer prior to metastasis greatly increases the efficacy of treatment and the chances of patient survival. Although numerous biomarkers have been reported to identify aggressive tumor types and predict prognosis, each biomarker is specific for a particular type of cancer, and no universal marker that can predict metastasis in a number of cancers have been identified. In addition, due to a lack of reliability, several markers are typically required to determine the prognosis and course of therapy.

Available for licensing are carboxypeptidase E (CPE) inhibitor compositions and methods to prognose and treat cancer as well as methods to determine the stage of cancer. The inventors discovered that CPE expression levels increase according to the presence of cancer and metastasis wherein CPE is upregulated in tumors and CPE levels are further increased in metastatic cancer. This data has been demonstrated both in vitro and in vivo experiments and in liver, breast, prostate, colon, and head and neck cancers. Metastatic liver cells treated with CPE siRNA reversed the cells from being metastatic and arrested cells from further metastasis. Thus, CPE as a biomarker for predicting metastasis and its inhibitors have an enormous potential to increase patient survival. CRADA Opportunity: The National Institute for Child Health and Human Development, Section on Cellular Neurobiology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize CPE as a biomarker for predicting metastasis. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Anti-Plasmodium Compositions and Methods of Use

Tue, 02 Dec 2008 02:00:00 GMT
The present invention comprises peptides/antibodies specific for the binding proteins of Plasmodium, a parasite responsible for malaria, hence in effect blocking the parasite’s binding to the erythrocytes. Also included are methods for their use in preventing, diagnosing or treating the related infections.

Although malaria is virtually eradicated in the United States, it continues to be one of the most serious infectious diseases in the world, killing millions of people each year in the countries throughout Africa, Asia and Latin America. In fact, over 41% of the world population lives in the regions affected by malaria. In vitro studies using the antibodies described in the current technology showed ~80% reduction in the number of blood cells infected with Plasmodium parasite. Infectivity studies using peptides demonstrated that they are also specifically able to prevent binding of parasites to blood cells. The claimed antibodies and peptides can also be used for immunization of humans and animals, or for development of diagnostic kits capable of detecting the presence, localization and quantity of the Plasmodium parasites in tissues and cells. CRADA Opportunity: The NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize "Anti-Plasmodium Compositions and Methods of Use." Please contact Dana Hsu at 301-496-2400 for more information.

Discovery of Novel Pharmacophores Inhibiting the Growth of Mycobacterium tuberculosis

Mon, 01 Dec 2008 07:00:00 GMT
Tuberculosis (TB) caused by Mycobacterium tuberculosis infects roughly one third of the world population and approximately 8 million people develop TB annually. The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) TB strains highlight the need for new drugs against TB. The inventions described herein are small molecules with drug-like properties that inhibit the growth of Mycobacterium tuberculosis. The compounds were discovered utilizing high-throughput screening of a 101,000 compound library. Three hundred active compounds inhibit Mycobacterium tuberculosis growth by 90% or greater in in vitro assays with MIC values ranging from 1.6 to less than 0.1 micrograms/ml, and showing minimal toxicity in tissue culture cells. Structure similarity analyses of the compounds reveal 44 chemical clusters representing 250 active compounds. CRADA Opportunity: The NIAID, OTD, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this "Discovery of Novel Pharmacophores Inhibiting the Growth of Mycobacterium Tuberculosis". Please contact Anna Amar at 301-451-3525 for more information.

A Novel, Non-Invasive and Therapeutically Useful High Throughput Technique to Isolate Highly Enriched Tumor Reactive Lymphocytes from Peripheral Blood - Potential Use in Adoptive Immunotherapy

Mon, 01 Dec 2008 12:00:00 GMT
The adoptive transfer of autologous antigen reactive lymphocytes has been shown to mediate significant tumor regression in some patients with metastatic cancer. However, the isolation of these T lymphocytes requires invasive surgery, which can lead to post-operative complications and delays in initiating adoptive immunotherapy with T cells.

This technology is directed to the use of a novel high throughput technique to isolate highly enriched tumor reactive lymphocytes in a non-invasive manner from the peripheral blood of cancer patients for the purpose of cancer immunotherapy. The technique utilizes a highly sensitive PCR based screening assay. CRADA Opportunity: The National Cancer Institute, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this high throughput T cell isolation technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Ectopic Thymidylate Synthase Accelerates the Development of Hyperplastic Foci and Adenomas in Pancreatic Islets

Mon, 01 Dec 2008 17:00:00 GMT
Thymidylate synthase (TS) is an E2F1-regulated enzyme essential for DNA synthesis and repair. Elevated levels of TS protein and mRNA levels are associated with many human cancers. Previous research by the NIH inventors has demonstrated that ectopic expression of catalytically active TS is sufficient to induce a transformed phenotype in mammalian cells as manifested by foci formation, anchorage independent growth, and tumor formation in nude mice. Overexpression of hTS in murine islets provides a model to study genetic alterations associated with the progression from normal cells to hyperplasia and adenoma and suggests that this mouse model may be useful for cancer prevention and the development of therapeutic strategies. CRADA Opportunity: The National Cancer Institute, Medical Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the Thymidylate Synthase Transgenic Animal Model. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Method for Detection of Cancer Based on Spatial Genome Organization in the Cell Nucleus

Mon, 01 Dec 2008 22:00:00 GMT
The successful treatment of cancer is correlated with the early detection of the cancerous cells. Conventional cancer diagnosis is largely based on qualitative morphological criteria, but more accurate quantitative tests could greatly increase early detection of malignant cells. It has been observed that the spatial arrangement of DNA in the nucleus is altered in cancer cells in comparison to normal cells. Therefore, it is possible to distinguish malignant cells by mapping the position of labeled marker genes in the nucleus.

This NIH invention provides methods of detecting abnormal cells in a sample using the spatial position of one or more genes within the nucleus of a cell, as well as a kit for detecting abnormal cells using such methods. The invention also provides methods of identifying gene markers for abnormal cells using the spatial position of one or more genes within the nucleus of a cell. CRADA Opportunity: The National Cancer Institute, Cell Biology of Genomes Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic methods for detection of cancer using spatial genome organization. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Compositions and Methods for Inhibition of Fat-Specific Protein 27

Tue, 02 Dec 2008 03:00:00 GMT
FSP27 expression is regulated by PPARgamma, a gene known to play a critical role in the development of fatty liver. Over-expression of FSP27 results in an increase in triglyceride accumulation and an increase in cystolic vacuoles containing lipid droplets which are associated with development of fatty liver disease or hepatic steatosis. This abnormal retention of lipids in liver cells occurs in diabetes and alcoholism and is correlated with decreased liver function which can often lead to cirrhosis and sometimes death. Presently, there are no adequate therapies for fatty liver disease.

This technology is directed towards compositions and methods of inhibiting FSP27, which include antisense compounds, small molecule inhibitors and antibodies that target FSP27. CRADA Opportunity: The Laboratory of Metabolism, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize inhibitors of FSP27 for treatment of fatty liver disease. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

A Varicella-Zoster Virus Mutant that is Markedly Impaired for Latent Infection Available for the Development of Shingles Vaccines and Diagnostics

Mon, 01 Dec 2008 08:00:00 GMT
Reactivation of latent Varicella-Zoster virus (VZV) infection is the cause of shingles, which is prominent in adults over the age of 60 and individuals who have compromised immune systems, due to HIV infection, cancer treatment and/or transplant. Shingles is a worldwide health concern that affects approximately 600,000 Americans each year. The incidence of shingles is also high in Europe, South America, and India; the latter having an estimated two million individuals affected, yearly. Recent research studies show that VZV vaccines have a significant effect on decreasing the incidence of shingles in elderly.

The current technology describes compositions, cells and methods related to the production and use of a mutant VZV and the development of vaccines against the infectious agent. Latent VZV expresses a limited repertoire of viral genes including the following six open reading frames (ORFs): 4, 21, 29, 62, 63, and 66. The present invention describes an ORF29 mutant VZV that demonstrates a weakened ability to establish latency in animal studies. The current technology provides methods for using the mutant in the development of live vaccines and diagnostic tools. A related invention is described in PCT/US05/021788 (publication number WO2006012092). CRADA Opportunity: The NIAID Laboratory of Clinical Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize vaccine strains of VZV vaccine with impaired latency. Please contact Jason Freeman, J.D., at 301/451-5054 or freemanch@mail.nih.gov for more information.

Methods and Compositions for Selectively Enriching Microbes

Mon, 01 Dec 2008 13:00:00 GMT
The described technology provides markedly improved enrichment of E. coli O157:H7, Shiga toxin-producing E. coli (STEC) and Shigella. This improved enrichment can be complimentary to, and enhance performance of, existing nucleic acid or antibody based detection methods. In addition, the improved enrichment method facilitates isolation of pathogens following positive results by any nucleic acid or antibody based test. Such isolation by cultural methods is essential for epidemiology, antibiotic sensitivity testing and other biochemical characterization.

Current enrichment protocols are often inadequate as they allow large numbers of interfering bacteria to grow. This makes it necessary for microbiologists to screen hundreds of presumptive colonies to achieve successful isolation (A Khan et al., Emerg Infect Dis. 2002 Jan; 8:54-62). The new technology is a simple two step process. The sample is first placed in a low pH solution for a brief period and then transferred to a medium permitting maximal growth of target bacteria. With this new technology there is no risk of false negative results due to inadvertent inhibition of target bacteria by novobiocin, tellurite, cefixime, or other additives commonly used in existing enrichment procedures.

This new technology has been shown to be effective with food, water, environmental and clinical samples. Its components are inexpensive and microbiologists are not required to impede their workflow by adding separate selective agents at specified intervals such as four or six hours. CRADA Opportunity: The FDA is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods for detecting pathogenic bacteria, especially E. coli O157:H7, Shiga toxin-producing E. coli (STEC) and Shigella. Please contact Alice Welch at Alice.Welch@fda.hhs.gov for more information.

Discovery of and Use of Fragments of DOC1 as Antiangiogenic and Antitumor Therapy

Sat, 01 Nov 2008 17:00:00 GMT
This invention describes small cDNA fragments of the coding region for wild type filamin A interacting protein 1-like (FILIP1L), previously known as down-regulated in ovarian cancer 1-like (DOC1) and variant 2 of FILIP1L genes that encode proteins that result in the inhibition of cell migration and motility, induce cell apoptosis and inhibit cell proliferation. These effects can be seen on endothelial cells and on tumor cells. These coding sequences have successfully been delivered to endothelial cells and tumor cells both in vitro and in vivo, and have demonstrated significant anti-tumor activity. In addition, the inventors have for the first time expressed the recombinant protein and developed antibodies to detect the protein fragments by Western, ELISA and immunohistochemistry. The significance of this invention is that it could provide for a series of new anti-cancer therapeutics and for the diagnostic means to follow their expression levels. CRADA Opportunity: The National Cancer Institute Hatfield Clinical Research Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Discovery of and Use of Fragments of DOC1 as Antiangiogenic and Antitumor Therapy. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Indoline Compounds for the Treatment of Spinal Muscular Atrophy (SMA) and Other Diseases

Sat, 01 Nov 2008 21:00:00 GMT
With the goal to treat SMA in patients, several indoline compounds were made and tested for activity. Tests in cells demonstrate that these drugs increased the levels of active SMN protein. This is encouraging since low levels of this protein appears to be the cause of neuronal death that leads to SMA. This class of compounds appears to operate via read-through of a non-sense stop-codon to produce full length, functional protein in SMA models. This mechanism may have utility in several other neurological disorders, including cystic fibroses and Duchene’s Muscular Dystrophy.

In addition, these compounds have also been shown to increase the concentration of a glutamate transporter protein in cells, which acts to recover glutamate back into neurons after release. Since the toxic effect of unrecovered excess glutamate is observed in many notorious neurological conditions, these compounds have potential for prevention or treatment. CRADA Opportunity: The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize drugs for the treatment of SMA, as well as investigation into novel uses for these indoline compounds. Please contact Dr. Melissa Maderia at maderiam@mail.nih.gov or 301-451-3943 for more information.

Human Monoclonal Antibodies Against Yersinia pestis

Sun, 02 Nov 2008 01:00:00 GMT
The technology describes a group of three (3) human monoclonal antibodies directed against the Yersinia pestis (Y. pestis) bacterium, the etiologic pathogen of the fatal disease Plague. These antibodies are specifically directed against two of the bacterium’s virulent factors, the F1 capsid protein (one antibody) and the low-calcium response antigen V (LcrV) (two antibodies). The antibodies have been shown to provide protection against Y. pestis challenge in a mouse model, with the highest protection attained with a combination of all three. The NIH offers the subject antibodies for licensing primarily for the development of therapeutic and/or prophylactic treatment against Y. pestis infections. Additionally, the antibodies may find use in research related to the pathogenicity of Y. pestis as well as for the development of new treatment against this pathogen.

Although human plague in the United States has occurred as mostly scattered cases in rural areas (an average of 10 to 15 persons each year), and globally, according to the World Health Organization there are only 1,000 to 3,000 cases of plague every year, it is however of significant importance to develop effective treatment against the plague disease, because of its biodefense significance. Y. pestis is included in the CDC and NIH’s category A agents that can be readily used as a biological weapon in the hand of bioterrorists. CRADA Opportunity: The National Cancer Institute CCRNP, Protein Interactions Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize human monoclonal antibodies against Yersinia pestis. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Treatment and Prevention of Age-Related Macular Degeneration and Other Eye-Related Diseases

Sat, 01 Nov 2008 05:00:00 GMT
The retinal pigment epithelium (RPE) plays a significant role in regulating the microenvironment around the photoreceptors in the distal retina, where the events of phototransduction take place.

Expression profiling of microRNA (miRNAs) in RPE and the adjacent retina and choroid was used to identify six miRNAs enriched in RPE. The potential use of anti-miRNAs specifically directed against miRNA 204 and miRNA 211 to prevent epithelial cell differentiation, proliferation and migration is disclosed. The miRNA 204 and miRNA 211 play a critical role in the control transepithelial electrical resistance. This technology further describes the significance of miRNAs in regulating junctional complexes in epithelial cells.

The claims in the pending patent application are directed towards methods and compositions containing anti-miRNAs or miRNA mimics for preventing or treating detrimental epithelial cell proliferation or loss of epithelial cell differentiation. CRADA Opportunity: The National Eye Institute, Section on Epithelial and Retinal Physiology and Disease, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of RPE-specific micro RNAs or anti-miRNAs or miRNA mimics for the treatment and prevention of age-related macular degeneration (AMD) and proliferative vitreal retinopathy, and more generally for preventing or treating detrimental epithelial cell proliferation or loss of epithelial cell differentiation, e.g., in the treatment and prevention of neovascular diseases and carcinoma.. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Methods for Using Interferon Gamma to Absorb Fluid From the Subretinal Space

Sat, 01 Nov 2008 09:00:00 GMT
The accumulation of subretinal fluid is associated with certain adverse ocular conditions (including chronic macular edema, age related macular degeneration, and diabetic retinopathy), or retinal injury, or post-surgical complications. Often aberrant proliferation and migration of retinal pigment epithelial (RPE) cells is also associated with these ocular conditions. The RPE is a highly specialized derivative of the neuroectoderm with multiple roles in the maintenance of normal ocular function. Dysfunction of RPE cells has been implicated in inflammatory, degenerative, and dystrophic diseases of the retina and choroid. Interferon gamma (IFN gamma) has been implicated in the pathogenesis of a number of intraocular inflammatory diseases of infectious or presumed autoimmune origin. IFN gamma has been detected in vitreous aspirates of patients with uveitis, proliferative vitreoretinopathy, and idiopathic inflammatory eye diseases.

The technology provides for methods by which interferon-gamma (IFN-gamma) can be used to remove subretinal fluid. The application of INF-gamma may be by external application (e.g. eye drops or ointments) or by subretinal injection. The claims in the pending patent application are directed to methods for treating decreases in visual acuity that are associated with diseases that cause the accumulation of fluid in the subretinal space. Additional claims are directed at methods for treating age-related macular degeneration, chronic macular edema, diabetic retinopathy, retinal detachment, or glaucoma that comprise decreasing the amount of fluid present in the subretinal space of patients suffering from such disorders by administering an amount of interferon gamma to the eyes of the patients effective to decrease the amount of fluid present in the subretinal space of the patients. CRADA Opportunity: The National Eye Institute, Section on Epithelial and Retinal Physiology and Disease, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods that activate immune system mediated fluid removal from the distal retina. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Induced Internalization of Surface Receptors to Disrupt Cell Surface Signaling

Sat, 01 Nov 2008 13:00:00 GMT
Cell-surface receptors are responsible for the biological activities of many molecules. Specific ligands bind to them, causing the cell-surface receptors to internalize or bring the receptor and ligand inside the cell. A number of diseases, including cancer, metabolic disorders, and viral infections are known to require the expression of cell-surface receptors for critical pathogenetic steps. This has prompted significant research efforts towards the development of pharmaceutical agents that block the signals from cell-surface receptors. While this current research shows great promise, there is a strong need for new therapeutic strategies that utilize the mechanistic properties of cell-surface receptors.

This technology describes a strategy for artificially inducing the internalization of surface receptors, and thereby blocking the effects of the ligands associated with that receptor. This method employs bifunctional ligands that bind to both a scavenger receptor and a target receptor. As proof of concept, the inventors Drs. Narazaki and Tosato have shown that a ligand capable of binding to the scavenger receptor SREC-1 and the neuropilin-1 receptor NRP1 induces the internalization of NRP1 and inhibits NRP1 signaling. The inventors propose that this strategy can be used to inhibit signaling from any target receptor if an appropriate bifunctional ligand is used. For example, the concept could be expanded to other receptors, such as HDL and LDL receptors. Likewise the bifunctional ligand could include specific antibodies or modified ligands that recognize cell surface receptors of biological importance. Accordingly, this approach could be used to limit tumor angiogenesis, limit tumor growth, block metastasis formation, block inflammation, block viral infection, and treat just about any disease where we identify a cell surface receptor an the molecular basis for disease. CRADA Opportunity: The National Cancer Institute, Laboratory of Cellular Oncology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the technology aimed at promoting selective receptor internalization as a means to neutralize ligand function and receptor signaling. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

A Simple Genetic Test for Kidney Disease

Sat, 01 Nov 2008 17:00:00 GMT
This technology relates to methods of diagnosing a predisposition to diseases that cause chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Variations in a gene, non-muscle myosin IIA (MYH9), are associated with 79% of the risk of focal segmental glomerulosclerosis (FSGS), the disease that causes ESKD, in African Americans with HIV, and 56% of African Americans as a whole. The variants are also associated with a 2-3 fold increased risk for ESKD associated with hypertension. The variations are also present among European Americans, although they are less common.

A simple genetic screening test has been developed that identifies single nucleotide polymorphisms (SNP) and haplotypes in the non-muscle myosin gene MYH9. These variants confer genetic risk for the following kidney diseases: FSGS, collapsing glomerulopathy, HIV-associated nephropathy, hypertensive kidney disease, sickle cell nephropathy, lupus nephropathy, and possibly other kidney diseases. CRADA Opportunity: The National Cancer Institute, Laboratory of Genomic Diversity, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize genetic testing for MYH9. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Fully Human Anti-Human Monoclonal Antibody Helpful in Developing Therapies Against Autoimmune and Infectious Diseases and Cancer

Sat, 01 Nov 2008 21:00:00 GMT
Available for licensing is a fully human monoclonal antibody (KYK-2.0 IgG1) with high specificity and affinity to human NKG2D, a stimulatory or costimulatory receptor located on the cell surface of natural killer (NK) cells and CD8+ T cells. NKG2D plays a role in mediating immune responses in autoimmune and infectious diseases and cancer and it makes NKG2D an attractive target for therapeutic intervention. Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been available. In solution, KYK-2.0 IgG1 interferes with the cytolytic activity of human NK cells. When immobilized, KYK-2.0 IgG1 induces human NK cell activation. The dual antagonistic and agonistic activity promises a broad range of therapeutic applications. CRADA Opportunity: The Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the fully human anti-human NKG2D monoclonal antibody KYK-2.0 IgG1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Predictive Test for Age-Related Macular Degeneration in Asymptomatic Individuals

Sun, 02 Nov 2008 01:00:00 GMT
Age-related macular degeneration (ARMD) is the leading cause of severe, irreversible vision loss for those over the age of fifty in the United States and in other developed countries. Thirteen million Americans over the age of forty have ARMD. ARMD is caused by the deterioration of the central area of the retina, or macula, resulting in a loss of central vision. This disease is believed to be a multigenic disorder, and is triggered by environmental factors such as smoking, age or diet in genetically susceptible individuals.

The present invention describes a highly predictive genetic test for universal practical clinical use to identify individuals at increased risk for ARMD. It comprises a rapid, accurate and affordable genetic screen, utilizing DNA microarray technology on a single chip. Sixteen genes are screened for 90 mutations/polymorphisms associated with ARMD, with a high predictive power (up to 92.7%) to identify asymptomatic carriers at risk. Accurate prediction of genetic susceptibility to this disorder will allow interventions to protect at-risk individuals. CRADA Opportunity: The NICHD Section on Clinical Genomics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Method Evolved for Recognition and Testing of Age-Related Macular Degeneration (MERT-ARMD). Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Molecular Motors Powered by Proteins

Sat, 01 Nov 2008 05:00:00 GMT
The technology available for licensing and commercial development relates to molecular motors powered by proteins. Some implementations describe a molecular motor in which multiple concentric cylinders or nested cones rotate around a common longitudinal axis. Opposing complementary surfaces of the cylinders or cones are coated with complementary motor protein pairs, such as actin and myosin. The actin and myosin interact with one another in the presence of ATP to rotate the cylinders or cones relative to one another, and this rotational energy is harnessed to produce work. Speed of movement is controlled by the concentration of ATP and the number of nested cylinders or cones. The length of the cylinders or cones can also be used to control the power generated by the motor.

Another configuration forms the motor out of a set of stacked disks, much like CDs on a spindle. The advantage of this form is extreme simplicity of construction compared to the nested cylinders or cones. In yet another configuration, which has aspects of both of the previous forms, the surfaces are broken into annular rings in order to overcome that the inner surfaces rotate at a different rate than the outer surfaces. This belt form may ultimately be used in molecular manufacturing. CRADA Opportunity: The National Cancer Institute, Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the Molecular Rotation Engine. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Matriptase Hypomorphic Mouse Model of a Human Ichthyosis

Wed, 01 Oct 2008 09:00:00 GMT
Available for licensing are mice with greatly reduced levels of matriptase, a membrane protease involved in epithelial development, immune function, and carcinogenesis. These mice were created to study autosomal recessive ichthyosis with hypotricosis (ARIH), an inherited human disease that has been linked to a mutation in the ST14 gene that encodes matriptase. These mice manifest the same defects seen in people afflicted by ARIH so it can be an effective model for studying the role of matriptase in disorders that affect skin development. CRADA Opportunity: The National Institute of Dental and Craniofacial Research, Oral and Pharyngeal Cancer Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or bradleyda@nidcr.nih.gov for more information.

Method of Treating and Preventing Infections in Immunocompromised Subjects with Immunostimulatory CpG Oligonucleotides

Wed, 01 Oct 2008 13:00:00 GMT
Primary disorders of the immune system can be divided into four categories, (1) disorders of the humoral immunity, (2) disorders of cellular immunity, (3) disorders of phagocytes, and (4) disorders of complement. In addition, there are many causes of secondary immunodeficiency such as treatment with immunosuppressive or chemotherapeutic agents, protein-losing enteropathy, and infection with a human immunodeficiency virus (HIV). Generally, immunocompromised patients are unable to mount an immune response to a vaccine or an infection in the same manner as non-immunocompromised individuals.

Opportunistic infections to which individuals infected with HIV are susceptible include bacterial infections such as salmonellosis, syphilis and neurosyphilis, tuberculosis (TB), a typical mycobacterial infection, and bacillary angiomatosis (cat scratch disease), fungal infections such as aspergillosis, candidiasis (thrush, yeast infection), coccidioidomycosis, cryptococcal meningitis, and histoplasmosis, protozoal infections such as cryptosporidiosis, isosporiasis, microsporidiosis, Pneumocystis Carinii pneumonia (PCP), and toxoplasmosis, viral infections such as Cytomegalovirus (CMV), hepatitis, herpes simplex (HSV, genital herpes), herpes zoster (HZV, shingles), human papilloma virus (HPV, genital warts, cervical cancer), Molluscum Contagiosum, oral hairy leukoplakia (OHL), and progressive multifocal leukoencephalopathy (PML), and neoplasms such as Kaposi's sarcoma, systemic non-Hodgkin's lymphoma (NHL), and primary CNS lymphoma, among others. These opportunistic infections remain principally responsible for the morbidity and mortality associated with HIV disease.

This application claims use of immunostimulatory D-type CpG oligonucleotides for the treatment of immunocompromised individuals. More specifically, the application claims use of immunostimulatory D-type CpG oligonucleotides for the treatment of individuals infected with HIV. CRADA Opportunity: The National Cancer Institute, Laboratory of Experimental Immunology, Immune Modulation Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Method of Treating Infectious and Inflammatory Lung Disease with Suppressive Oligonucleotides

Wed, 01 Oct 2008 17:00:00 GMT
Lung disease is the number three killer in America, responsible for one in seven deaths, and lung disease and other breathing problems are the number one killer of babies younger than one year old. Today, more than thirty (30) million Americans are living with chronic inflammatory lung diseases such as emphysema and chronic bronchitis. In addition, approximately one hundred and fifty thousand (150,000) Americans are affected by acute respiratory distress syndrome (ARDS) each year.

Many lung diseases are associated with lung inflammation. For example, ARDS involves the rapid onset of progressive malfunction of the lungs, and is usually associated with the malfunction of other organs due to the inability to take up oxygen. The condition is associated with extensive lung inflammation and small blood vessel injury in all affected organs. ARDS is commonly precipitated by trauma, sepsis (systemic infection), diffuse pneumonia, and shock. It also may be associated with extensive surgery, and certain blood abnormalities. In many cases of ARDS and other inflammatory lung diseases, the inflammatory response that accompanies the underlying disease state is much more dangerous than the underlying infection or trauma.

This application claims use of suppressive oligonucleotides to suppress lung inflammation. More specifically, the application claims use of suppressive oligonucleotides for the treatment, prevention, or inhibition of pneumonia, ARDS, and chronic bronchitis. CRADA Opportunity: The National Cancer Institute, Laboratory of Experimental Immunology, Immune Modulation Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Use of Suppressive Oligonucleotides to Treat Uveitis

Wed, 01 Oct 2008 21:00:00 GMT
Uveitis is a major cause of visual loss in industrialized nations. Uveitis refers to an intraocular inflammation of the uveal tract, namely, the iris, choroids, and ciliary body. Uveitis is responsible for about ten percent (10 %) of the legal blindness in the United States. Complications associated with uveitis include posterior synechia, cataracts, glaucoma and retinal edema.

Suppressive CpG oligodeoxynucleotides (ODNs) are ODNs capable of reducing an immune response, such as inflammation. Suppressive ODNs are DNA molecules of at least eight nucleotides in length, where the ODN forms a G-tetrad, and has a circular dichroism value greater than 2.9. In a suppressive ODN, the number of guanosines is at least two.

This application claims compositions and methods for the treatment of uveitis. Specifically, the application claims use of suppressive CpG ODNs to treat uveitis. The compositions and methods of the application can be used for the treatment of anterior, posterior and diffuse uveitis. CRADA Opportunity: The National Cancer Institute, Laboratory of Experimental Immunology, Immune Modulation Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Monoclonal Antibodies That Bind or Neutralize Dengue Virus

Thu, 02 Oct 2008 01:00:00 GMT
Among the arthropod-borne flaviviruses, the four dengue virus serotypes, dengue type 1 virus (DENV-1), dengue type 2 virus (DENV-2), dengue type 3 virus (DENV-3), and dengue type 4 virus (DENV-4 are most important in terms of human morbidity and geographic distribution. Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitoes are abundant. Dengue infection produces fever, rash, and joint pain in humans. A more severe and life-threatening form of dengue, characterized by hemorrhagic fever and hemorrhagic shock, has occurred with increasing frequency in Southeast Asia and Central and South America, where all four dengue virus serotypes circulate. A safe and effective vaccine against dengue is currently not available. Passive immunization with monoclonal antibodies from non-human primates or humans represents a possible alternative to vaccines for prevention of illness caused by dengue virus.

The application claims monoclonal antibodies that bind or neutralize dengue type 1, 2, 3, and/or 4 viruses. The application also claims fragments of such antibodies retaining dengue virus-binding ability, fully human or humanized antibodies retaining dengue virus-binding ability, and pharmaceutical compositions including such antibodies. The application also claims isolated nucleic acids encoding the antibodies of the invention. Additionally, application claims prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention. CRADA Opportunity: The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Ching-Juh Lai at 301-594-2422 for more information.

Beta 1,4-Galactosyltransferases with Altered Donor and Acceptor Specificities, Compositions and Methods of Use: Development of Pharmaceuticals and Improved Vaccines

Wed, 01 Oct 2008 05:00:00 GMT
The present invention relates to the field of glycobiology, specifically to glycosyltransferases. The present invention provides structure-based design of novel glycosyltransferases and their biological applications.

The structural information of glycosyltransferases has revealed that the specificity of the sugar donor in these enzymes is determined by a few residues in the sugar-nucleotide binding pocket of the enzyme, which is conserved among the family members from different species. This conservation has made it possible to reengineer the existing glycosyltransferases with broader sugar donor specificities. Mutation of these residues generates novel glycosyltransferases that can transfer a sugar residue with a chemically reactive functional group to N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus, there is potential to develop mutant glycosyltransferases to produce glycoconjugates carrying sugar moieties with reactive groups that can be used in the assembly of bio-nanoparticles to develop targeted-drug delivery systems or contrast agents for medical uses.

Accordingly, methods to synthesize N-acetylglucosamine linkages have many applications in research and medicine, including in the development of pharmaceutical agents and improved vaccines that can be used to treat disease.

The invention claims beta (1,4)-galactosyltransferase I mutants having altered donor and acceptor and metal ion specificities, and methods of use thereof. In addition, the invention claims methods for synthesizing oligosaccharides using the beta (1,4)-galactosyltransferase I mutants and to using the beta (1,4)-galactosyltransferase I mutants to conjugate agents, such as therapeutic agents or diagnostic agents, to acceptor molecules. More specifically, the invention claims a double mutant beta 1, 4 galactosyltransferase, human beta-1, 4-Tyr289Leu-Met344His-Gal-T1, constructed from the individual mutants, Tyr289Leu-Gal-T1 and Met344His-Gal-T1, that transfers modified galactose in the presence of magnesium ion, in contrast to the wild-type enzyme which requires manganese ion. CRADA Opportunity: The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize glycosyltransferases. Please contact John D. Hewes, Ph.D., Technology Transfer Specialist, NCI, at (301) 435-3121 or hewesj@mail.nih.gov for more information.

Alpha 1-3 N-Acetylgalactosaminyltransferases with Altered Donor and Acceptor Specificities, Compositions, and Methods of Use: Development of Pharmaceutical Agents and Improved Vaccines

Wed, 01 Oct 2008 09:00:00 GMT
The present invention relates to the field of glycobiology, specifically to glycosyltransferases. The present invention provides structure-based design of novel glycosyltransferases and their biological applications.

The structural information of glycosyltransferases has revealed that the specificity of the sugar donor in these enzymes is determined by a few residues in the sugar-nucleotide binding pocket of the enzyme, which is conserved among the family members from different species. This conservation has made it possible to reengineer the existing glycosyltransferases with broader sugar donor specificities. Mutation of these residues generates novel glycosyltransferases that can transfer a sugar residue with a chemically reactive functional group to N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus, there is potential to develop mutant glycosyltransferases to produce glycoconjugates carrying sugar moieties with reactive groups that can be used in the assembly of bio-nanoparticles to develop targeted-drug delivery systems or contrast agents for medical uses.

Accordingly, methods to synthesize N-acetylglucosamine linkages have many applications in research and medicine, including in the development of pharmaceutical agents and improved vaccines that can be used to treat disease.

This application claims compositions and methods based on the structure-based design of alpha 1-3 N-Acetylgalactosaminyltransferase (alpha 3 GalNAc-T) mutants from alpha l-3galactosyltransferase (a3Gal-T) that can transfer 2'-modified galactose from the corresponding UDP-derivatives due to mutations that broaden the alpha 3Gal-T donor specificity and make the enzyme alpha3 GalNAc-T. CRADA Opportunity: The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize structure-based design of novel glycosyltransferases. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Use of CpG Oligodeoxynucleotides to Induce Epithelial Cell Growth

Wed, 01 Oct 2008 13:00:00 GMT
Wound repair is the result of complex interactions and biologic processes. Three phases have been described in normal wound healing: acute inflammatory phase, extracellular matrix and collagen synthesis, and remodeling. The process involves the interaction of keratinocytes, fibroblasts and inflammatory cells at the wound site. The sequence of the healing process is initiated during an acute inflammatory phase with the deposition of provisional tissue. This is followed by re-epithelialization, collagen synthesis and deposition, fibroblast proliferation, and neovascularization, all of which ultimately define the remodeling phase. These events are influenced by growth factors and cytokines secreted by inflammatory cells or by the cells localized at the edges of the wound.

Tissue regeneration is believed to be controlled by specific peptide factors which regulate the migration and proliferation of cells involved in the repair process. Thus, it has been proposed that growth factors will be useful therapeutics in the treatment of wounds, burns and other skin disorders. However, there still remains a need for additional methods to accelerate wound healing and tissue repair.

This application claims methods of increasing epithelial cell growth. The methods include administering a therapeutically effective amount of a CpG oligodeoxynucleotide (ODN) to induce epithelial cell division. Also claimed are methods of inducing wound healing. The method includes treating the wound with a CpG oligonucleotide, thereby inducing wound healing. The wound can be any type of wound, including trauma or surgical wounds. The CpG ODN can be applied systemically or locally. CRADA Opportunity: The Laboratory of Experimental Immunology of the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of increasing epithelial cell growth. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Live Attenuated Virus Vaccines for La Crosse Virus and Other Bunyaviridae

Wed, 01 Oct 2008 17:00:00 GMT
La Crosse virus (LACV), family Bunyaviridae, is a mosquito-borne pathogen endemic in the United States. LACV infection results in 70–130 clinical cases a year and is the major cause of pediatric arboviral encephalitis in North America. LACV was first identified as human pathogen in 1960 after its isolation from a 4 year-old girl from Minnesota who suffered meningoencephalitis and later died in La Crosse, Wisconsin. The majority of LACV infections are mild and never reported, however serologic studies estimate annual infection rates of 10–30/100,000 in endemic areas. LACV is a member of the California serogroup of viruses in the genus Orthobunyavirus. The serogroup contains members found on five continents that include human pathogens such as La Crosse, Snowshoe hare, and Jamestown Canyon viruses in North America; Guaroa virus in North and South America; Inkoo and Tahyna viruses in Europe; and Lumbo virus in Africa. Children who recover from severe La Crosse encephalitis may have significantly lower IQ scores than expected and a high prevalence (60% of those tested) of attention-deficit-hyperactivity disorder. Seizure disorders are also common in survivors. LACV can also cause encephalitis in immunosuppressed adults. Projected lifelong economic costs associated with neurologic sequelae range from $48,775–3,090,398 per case. At present, a vaccine or FDA approved antiviral therapy is not available.

This application principally claims live attenuated LACV vaccine compositions, but also includes subunit vaccine compositions including California encephalitis virus (CEV) serogroup immunogens, attenuated and inactivated CEV serogroup and chimeric Bunyaviridae. Also claimed are methods of treating or preventing CEV serogroup infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a CEV serogroup immunogen, methods for detecting LACV infection in a biological sample and infectious chimeric Bunyaviridae. CRADA Opportunity: The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize live attenuated virus vaccine candidates for La Crosse virus and other Bunyaviridae. Please contact Dr. Whitehead at 301-496-7692 for more information.

Development of Antigenic Chimeric St. Louis Encephalitis Virus/Dengue Virus Type Four Recombinant Viruses (SLEV/DEN4) as Vaccine Candidates for the Prevention of Disease Caused by SLEV

Wed, 01 Oct 2008 21:00:00 GMT
St. Louis Encephalitis Virus (SLEV) is a mosquito-borne flavivirus that is endemic in the Americas and causes sporadic outbreaks of disease in humans. SLEV is a member of the Japanese encephalitis virus serocomplex and is closely related to West Nile Virus (WNV). St. Louis encephalitis is found throughout North, Central, and South America, and the Caribbean, but is a major public health problem mainly in the United States. Prior to the outbreak of West Nile virus in 1999, St. Louis encephalitis was the most common human disease caused by mosquitoes in the United States. Since 1964, there have been about 4,440 confirmed cases of St. Louis encephalitis, with an average of 130 cases per year. Up to 3,000 cases have been reported during epidemics in some years. Many more infections occur without symptoms and go undiagnosed. At present, a vaccine or FDA approved antiviral therapy is not available.

The inventors have previously developed a WNV/Dengue4Delta30 antigenic chimeric virus as a live attenuated virus vaccine candidate that contains the WNV premembrane and envelope (prM and E) proteins on a dengue virus type 4 (DEN4) genetic background with a thirty nucleotide deletion (Delta30) in the DEN4 3’-UTR. Using a similar strategy, the inventors have generated an antigenic chimeric virus, SLE/DEN4Delta30. Preclinical testing results indicate that chimerization of SLE with DEN4Delta30 decreased neuroinvasiveness in mice, did not affect neurovirulence in mice, and appeared to overattenuate the virus for non-human primates. Modifications of the SLE/DEN4Delta30 vaccine candidate are underway to improve its immunogenicity.

This application claims live attenuated chimeric SLE/DEN4Delta30 vaccine compositions and bivalent WNV/SLE/DEN4Delta30 vaccine compositions. Also claimed are methods of treating or preventing SLEV infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a SLEV immunogen, methods for detecting SLEV infection in a biological sample and infectious chimeric SLEV. CRADA Opportunity: The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize live attenuated virus vaccine candidates for St. Louis encephalitis virus. Please contact Dr. Whitehead at 301-496-7692 for more information.

Monoclonal Antibodies Against Orthopoxviruses

Thu, 02 Oct 2008 01:00:00 GMT
Concerns that variola (smallpox) virus might be used as a biological weapon have led to the recommendation of widespread vaccination with vaccinia virus. While vaccination is generally safe and effective for prevention of smallpox, it is well documented that various adverse reactions in individuals have been caused by vaccination with existing licensed vaccines. Vaccinia immune globulin (VIG) prepared from vaccinated humans has historically been used to treat adverse reactions arising from vaccinia immunization. However, VIG lots may have different potencies and carry the potential to transmit other viral agents.

Chimpanzee Fabs against the B5 and A33 outer extracellular membrane proteins of vaccinia virus were isolated and converted into complete mAbs with human gamma1 heavy chain constant regions. The two mAbs displayed high binding affinities to B5 and A33. The mAbs inhibited the spread of vaccinia virus as well as variola virus (the causative agent of smallpox) in vitro, protected mice from subsequent intranasal challenge with virulent vaccinia virus, protected mice when administered 2 days after challenge, and provided significantly greater protection than that afforded by VIG. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Chimpanzee/human neutralizing monoclonal antibodies against orthopoxviruses. Please contact Dr. Robert Purcell at 301-496 5090 for more information.

Methods of Glycosylation and Bioconjugation

Wed, 01 Oct 2008 05:00:00 GMT
Eukaryotic cells express several classes of oligosaccharides attached to proteins or lipids. Animal glycans can be N-linked via beta-GlcNAc to Asn (N-glycans), O-linked via -GalNAc to Ser/Thr (O-glycans), or can connect the carboxyl end of a protein to a phosphatidylinositol unit (GPI-anchors) via a common core glycan structure. Beta (1,4)-galactosyltransferase I catalyzes the transfer of galactose from the donor, UDP-galactose, to an acceptor, N-acetylglucosamine, to form a galactose-beta (1,4)-N-acetylglucosamine bond, and allows galactose to be linked to an N-acetylglucosamine that may itself be linked to a variety of other molecules. Examples of these molecules include other sugars and proteins. The reaction can be used to make many types of molecules having great biological significance. For example, galactose-beta (1,4)-N-acetylglucosamine linkages are important for many recognition events that control how cells interact with each other in the body, and how cells interact with pathogens. In addition, numerous other linkages of this type are also very important for cellular recognition and binding events as well as cellular interactions with pathogens, such as viruses. Therefore, methods to synthesize these types of bonds have many applications in research and medicine to develop pharmaceutical agents and improved vaccines that can be used to treat disease.

The invention provides in vitro folding method for a polypeptidyl-alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T) that transfers GalNAc to Ser/Thr residue on a protein. The application claims that this in vitro-folded recombinant ppGalNAc-T enzyme transfers modified sugar with a chemical handle to a specific site in the designed C-terminal polypeptide tag fused to a protein. The invention provides methods for engineering a glycoprotein from a biological substrate, and methods for glycosylating a biological substrate for use in glycoconjugation. Also included in the invention are diagnostic and therapeutic uses. CRADA Opportunity: The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Development of Dengue Virus Type 3 Vaccine Candidates

Wed, 01 Oct 2008 09:00:00 GMT
The disease burden associated with dengue virus infection has increased over the past several decades in the tropical and semi-tropical regions of the world, where over 2 billion people live at risk of dengue infection. Annually, there are an estimated fifty (50) to one hundred (100) million cases of dengue fever, making development of an effective vaccine a priority. In addition, there is a need for a "travelers vaccine" to protect those visiting dengue virus endemic areas, similar in scope to other currently available "travelers vaccines", such as hepatitis A vaccine.

The previously identified delta30 attenuating mutation, created in each dengue virus serotype by the removal of 30 homologous nucleotides from the 3'-UTR, is capable of attenuating wild-type strains of dengue virus type 1 (DEN1), type 4 (DEN4) and to a limited extent type 2 (DEN2). These DEN1delta30 and DEN4delta30 viruses have been shown to be both safe and immunogenic in humans. However, the delta30 mutation failed to have an attenuating effect on dengue virus type 3 (DEN3). To generate DEN3 vaccine candidates with a clearly attenuated phenotype, viruses were produced containing 3'-UTR deletions consisting of extensions of the original delta30 mutation or additional mutations which remove stem-loop structures similar to those removed by delta30. In addition, the entire 3'-UTR of DEN3 was replaced with the 3'-UTR derived from DEN4 and containing the delta30 mutation. Studies in monkeys demonstrated that these newly developed viruses are highly attenuated, yet sufficiently immunogenic to warrant their further development for use as live attenuated vaccine candidates. Such viruses are anticipated to become the DEN3 component of a tetravalent vaccine formulation designed to immunize against all four dengue virus serotypes. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or bm25f@nih.gov for more information.

Catalytic Domains of [beta](1,4)-galactosyltransferase I Having Altered Donor and Acceptor Specificities, Domains That Promote In Vitro Protein Folding, and Methods for Their Use

Wed, 01 Oct 2008 13:00:00 GMT
[beta](1,4)-galactosyltransferase I catalyzes the transfer of galactose from the donor, UDP-galactose, to an acceptor, N-acetylglucosamine, to form a galactose-[beta](1,4)-N-acetylglucosamine bond. This reaction allows galactose to be linked to an N-acetylglucosamine that may itself be linked to a variety of other molecules. The reaction can be used to make many types of molecules having great biological significance. For example, galactose-[beta](1,4)-N-acetylglucosamine linkages are very important for cellular recognition and binding events as well as cellular interactions with pathogens, such as viruses. Therefore, methods to synthesize these types of bonds have many applications in research and medicine to develop pharmaceutical agents and improved vaccines that can be used to treat disease.

The present invention is based on the surprising discovery that the enzymatic activity of [beta](1,4)-galactosyltransferase can be altered such that the enzyme can make chemical bonds that are very difficult to make by other methods. These alterations involve mutating the enzyme such that the mutated enzyme can transfer many different types of sugars from sugar nucleotide donors to many different types of acceptors. Therefore, the mutated [beta](1,4)-galactosyltransferases of the invention can be used to synthesize a variety of products that, until now, have been very difficult and expensive to produce.

The invention also provides amino acid segments that promote the proper folding of a galactosyltransferase catalytic domain and mutations in the catalytic domain that enhance folding efficiency and make the enzyme stable at room temperature. The amino acid segments may be used to properly fold the galactosyltransferase catalytic domains of the invention and thereby increase their activity. The amino acid segments may also be used to increase the activity of galactosyltransferases that are produced recombinantly. Accordingly, use of the amino acid segments according to the invention allows for production of [beta](1,4)-galactosyltransferases having increased enzymatic activity relative to [beta](1,4)-galactosyltransferases produced in the absence of the amino acid segments. CRADA Opportunity: The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of galactose and modified galactose to be linked to an N-acetylglucosamine that may itself be linked to a variety of other molecules. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.

Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1, 2, 3, and 4

Wed, 01 Oct 2008 17:00:00 GMT
The invention relates to a dengue virus tetravalent vaccine containing a common 30-nucleotide deletion (delta30) in the 3'-untranslated region (UTR) of the genome of dengue virus serotypes 1, 2, 3, and 4. The previously identified delta30 attenuating mutation, created in dengue virus type 4 (DEN4) by the removal of 30 nucleotides from the 3'-UTR, is also capable of attenuating a wild-type strain of dengue virus type 1 (DEN1). Removal of 30 nucleotides from the DEN1 3'-UTR in a highly conserved region homologous to the DEN4 region encompassing the delta30 mutation yielded a recombinant virus attenuated in rhesus monkeys to a level similar to recombinant virus DEN4delta30. This established the transportability of the delta30 mutation and its attenuation phenotype to a dengue virus type other than DEN4. The effective transferability of the delta30 mutation establishes the usefulness of the delta30 mutation to attenuate and improve the safety of commercializable dengue virus vaccines of any serotype.

A tetravalent dengue virus vaccine containing dengue virus types 1, 2, 3, and 4 each attenuated by the delta30 mutation is being developed. The presence of the delta30 attenuating mutation in each virus component precludes the reversion to a wild-type virus by intertypic recombination. In addition, because of the inherent genetic stability of deletion mutations, the delta30 mutation represents an excellent alternative for use as a common mutation shared among each component of a tetravalent vaccine. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or bm25f@nih.gov for more information.

Live Attenuated Vaccine to Prevent Disease Caused by West Nile Virus

Wed, 01 Oct 2008 21:00:00 GMT
WNV has recently emerged in the U.S. and is considered a significant emerging disease that has embedded itself over a considerable region of the U.S. WNV infections have been recorded in humans as well as in different animals. To date, WNV has killed 294 people in the U.S. and caused severe disease in more than 4222 others. This project is part of NIAID’s comprehensive emerging infectious disease program, which supports research on bacterial, viral, and other types of disease-causing microbes.

The methods and compositions of this invention provide a means for prevention of WNV infection by immunization with attenuated, immunogenic viral vaccines against WNV. The invention involves a chimeric virus form consisting of parts of WNV and Dengue virus. Construction of the hybrids and their properties are described in detail in AG Pletnev et al., PNAS 2002;99(5):3036-3041.

The WNV chimeric vaccine does not target the central nervous system, which would be the case in an infection with wild type WNV. The vaccine stimulates strong anti-WNV immune responses, even following a single dose of the vaccine. When injected into mice, the vaccine protected all of the immunized animals from subsequent exposure to the New York WNV strain. The vaccine was also effective in primates. Researchers intend to begin human trials in late 2003.

The WNV vaccine may be used to protect the human population, particularly the elderly people, and domestic animals from WNV infection in the affected regions of the U.S. as well as worldwide. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, and commercialize this technology. Please contact Percy Pan at 301-451-3523 or panp@niaid.nih.gov for more information.

Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses

Thu, 02 Oct 2008 01:00:00 GMT
Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. This invention relates to dengue virus mutations that may contribute to the development of improved dengue vaccines. Site directed and random mutagenesis techniques were used to introduce mutations into the dengue virus genome and to assemble a collection of useful mutations for incorporation in recombinant live attenuated dengue virus vaccines. The resulting mutant viruses were screened for several valuable phenotypes, including temperature sensitivity in Vero cells or human liver cells, host cell restriction in mosquito cells or human liver cells, host cell adaptation for improved replication in Vero cells, and attenuation in mice or in mosquitoes. The genetic basis for each observed phenotype was determined by direct sequence analysis of the genome of the mutant virus. Mutations identified through these sequencing efforts have been further evaluated by re-introduction of the identified mutations, singly, or in combination, into recombinant dengue virus and characterization of the resulting recombinant virus for phenotypes. In this manner, a menu of attenuating and growth promoting mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccine candidates. The mutations promoting growth in Vero cells have usefulness for the production of live or inactivated dengue virus vaccines. CRADA Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or bm25f@nih.gov for more information.

Modified Sugar Substrates and Methods of Use

Mon, 01 Sep 2008 05:00:00 GMT
Glycans can be classified as linear or branched sugars. The linear sugars are the glycosaminoglycans comprising polymers of sulfated disaccharide repeat units that are O-linked to a core protein, forming a proteoglycan aggregate. The branched glycans are found as N-linked and O-linked sugars on glycoproteins or on glycolipids. These carbohydrate moieties of the linear and branched glycans are synthesized by a super family of enzymes, the glycosyltransferases (GTs), which transfer a sugar moiety from a sugar donor to an acceptor molecule. Although GTs catalyze chemically similar reactions in which a monosaccharide is transferred from an activated derivative, such as a UDP-sugar, to an acceptor, very few GTs bear similarity in primary structure.

Eukaryotic cells express several classes of oligosaccharides attached to proteins or lipids. Animal glycans can be N-linked via beta-GlcNAc to Asparagine (N-glycans), O-linked via UDP-GalNAc to Serine/Threonine (O-glycans), or can connect the carboxyl end of a protein to a phosphatidylinositol unit (GPI-anchors) via a common core glycan structure. Thus, there is potential to develop carbohydrate substrates comprising bioactive agents that can be used to produce glycoconjugates carrying sugar moieties with bioactive agents. Such glycoconjugates have many therapeutic and diagnostic uses, e.g. in labeling or targeted delivery. Further, such glycoconjugates can be used in the assembly of bio-nanoparticles to develop targeted-drug delivery systems or contrast agents for medical uses.

This application claims methods and compositions for making and using functionalized sugars. Also claimed in the application are methods for forming a wide variety of products at a cell or in an in vitro environment. More specifically, the claimed compositions of the invention comprise a sugar nucleotide and one or more functional groups. CRADA Opportunity: The National Cancer Institute’s Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the synthesis of UDP derivatives of C2 modified galactose for use as donor substrates for glycosyltransferases. Please contact John D. Hewes, Ph.D. at 301-435-3121 or < a href="mailto:hewesj@mail.nih.gov">hewesj@mail.nih.gov for more information.

A Novel Treatment for Malarial Infections

Mon, 01 Sep 2008 09:00:00 GMT
The inventions described herein are antimalarial small molecule inhibitors of the plasmodial surface anion channel (PSAC), an essential nutrient acquisition ion channel expressed on human erythrocytes infected with malaria parasites. These inhibitors were discovered by high-throughput screening of chemical libraries and analysis of their ability to kill malaria parasites in culture. Two separate classes of inhibitors were found to work synergistically in combination against PSAC and killed malaria cultures at markedly lower concentrations than separately. These inhibitors have high affinity and specificity for PSAC and have acceptable cytotoxicity profiles. Preliminary in vivo testing of these compounds in a mouse malaria model is currently ongoing. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antimalarial drugs that target PSAC or other parasite-specific transporters. Please contact Dana Hsu at 301-496-2644 for more information.

Human-Bovine Chimeric Respiratory Syncytial Virus (RSV) Vaccines

Mon, 01 Sep 2008 13:00:00 GMT
Available for licensing and commercial development is a patent estate and related biological materials for making human-bovine chimeric virus particles for formulating live attenuated vaccines against human respiratory syncytial virus (RSV). Chimeric human-bovine RSVs are recombinantly engineered to incorporate nucleotide sequences from both human and bovine RSV strains and produce infectious, chimeric viruses that elicit anti-RSV immunological responses in humans and non-human primates. The chimeras incorporate partial or complete human or bovine RSV background genomes with one or more recombinantly integrated heterologous genes or genome segments of a different RSV strain.

Heterologous genes of interest for making chimeric recombinants include NS1, NS2, N, P, M, SH glycoprotein (or an immunogenic domain or epitope thereof), M2(ORF1), M2(ORF2), L, F or G genes or a genome segment including a protein or portion thereof or alternatively a leader, trailer or intergenic region of the RSV genome, or a segment thereof. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric RSV of the invention to yield desired phenotypic and structural effects. Exemplary human-bovine chimeric RSV of the invention incorporate a chimeric RSV genome or antigenome comprising both human and bovine polynucleotide sequences, as well as a major nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large polymerase protein (L), and a RNA polymerase elongation factor. Additional RSV proteins may be included in various combinations to provide a range of infectious subviral particles up to a complete viral particle or a viral particle containing supernumerary proteins, antigenic determinants or other additional components. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize attenuated live vaccines against respiratory syncytial virus (RSV). Please contact Barry Buchbinder at 301-594-1696 for more information.

Respiratory Syncytial Virus (RSV) Vaccines Based on Promoter-Proximate Attenuation

Mon, 01 Sep 2008 17:00:00 GMT
Available for licensing and commercial development is a patent estate and related biological materials for producing therapeutic or prophylactic vaccines against Respiratory Syncytial Virus (RSV). The claimed vaccine strategy relates to the engineering and creation of live-attenuated RSV vaccine candidates by shifting the position of one or more viral genes relative to the viral promoter (aka promoter-proximal attenuation). The gene shifts can be constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome. Viral replication can increase or decrease depending on the position of expressed viral gene and depending on the nature and degree of the positional shift. Viral gene rearrangements are selected to maintain sufficient non-infectious replication of RSV while eliciting host anti-RSV immune responses. Viral genes targeted for such rearrangement include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or genome segment.

One modification of particular interest is the placement of the G and F protective antigen genes in a promoter-proximal position for increased expression. The gene position-shifted RSV can be further manipulated by the addition of specific nucleotide and amino acid point mutations or host range restriction determinants to yield desired phenotypic and structural effects. CRADA Opportunity: The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize live attenuated vaccines. Please contact Michael Piziali at 301-451-3527 for more information.